目的：本研究旨在探讨人核心聚糖蛋白decorin是否可以缓解糖尿病心肌病并对其中机制进行探索。方法：在本研究中，采用Wistar大鼠作为研究对象，通过腹腔注射链唑霉素并采用高脂饮食喂养6个月诱导糖尿病心肌病模型。通过重组腺相关病毒介导大鼠心脏高表达decorin。在体外研究中，通过高浓度葡萄糖模拟在体高血糖刺激，并在人脐静脉内皮细胞中高表达decorin，通过研究细胞凋亡水平、成管能力、迁移能力和增殖能力，观察其对内皮细胞的保护效应。结果：结果显示，糖尿病心肌病大鼠表现为毛细血管密度减低、心肌纤维化以及心脏功能受损，而过表达decorin可以促进血管内皮生长因子（ VEGF）的表达，增加血管密度，减轻心肌纤维化并缓解糖尿病心肌病大鼠的心脏功能。同时，体外研究结果也表明，高糖可以抑制IGF1R／AKT通路，抑制VEGF的表达，诱导内皮细胞的凋亡增加，抑制细胞的成管能力、迁移能力和增殖能力，而过表达deco－rin则缓解了上述效应。另外，抗IGF1R抗体预处理或者AKT抑制剂处理可以阻断decorin的保护作用。结论：Decorin可以通过激活IGF1R／AKT通路，上调VEGF的表达并促进血管生成，从而缓解糖尿病心肌病。
作者：唐家荣；赖金胜；陈复琼 刊期： 2016年第08期
AIM:The 50-Hz magnetic field (MF) is a potential health-risk factor.Its effects on the cardiovascular system have not been fully investigated .This study was conducted to explore the effects of long-term exposure to 50-Hz MF on the cardiovascular system . METHODS:In the study , an exposure system was constructed and the distribution of 50-Hz MF was detected .Sixty-four Sprague-Dawley (SD) rats were exposed to 50-Hz MF at 100 μT for 24 weeks, 20 hours per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks, and 24 weeks later, echocardiography, cardiac catheterisation and electrocardiography were performed .Moreover , heart and body weight were recorded , while haematoxylin-eosin staining and real-time PCR were conducted .RESULTS:The results showed that compared with the sham group , exposure to 50-Hz MF did not exert any effect on blood pressure, pulse rate, heart rate and cardiac rhythm.Further, echocardiography and cardiac catheterisation showed that there were no significant differences in the cardiac morphology and haemodynamics .In addition , histopathological examination showed that 50-Hz MF exposure had no effect on the structure of hearts .Finally, the expression of the cardiac hypertrophic relative genes did not show any significant differences between 50-Hz MF exposure group and the sham group .CONCLUSION: Taken together , in SD rats, exposure to 50-Hz/100-μT MF for 24 weeks did not show any obvious effects on the cardiovascular system .
作者： 刊期： 2016年第08期
目的：观察超声心动图斑点追踪方法能否早期发现和诊断异丙基肾上腺素（isoprenaline，ISO）引起的心脏功能异常。方法：将成年C57雄性小鼠分为对照组、ISO给药后3 d组和ISO给药后7 d组3组（ n＝6）。 ISO组均为一次性给予ISO 5 mg／kg皮下注射，对照组给予生理盐水皮下注射，分别于给药后3d和7d应用传统超声心动图方法以及斑点追踪方法评价小鼠心脏功能。结果：包括径向应变（radial strain，RS）、径向应变率（radial strain rate，RSR）和纵向应变（longitudinal strain，LS）在内的心脏应变分析指标，均在ISO注射后3 d开始显著降低。另外，与心肌梗死的局灶性改变不同，ISO诱导的心肌肥厚在应变分析中表现为全心功能的异常。而相比之下，传统超声心动图仅能在ISO注射后7 d检测出E／E’显著升高，提示心脏舒张功能异常，而反映收缩功能的左室短轴缩短率（ FS），以及反映心脏舒张功能的另外2个指标E／A和E’／A’均无显著差异。此外，心脏应变异常仅发生在ISO诱导的病理性心肌肥厚中，而并不出现在跑步训练诱导的生理性心肌肥厚中。结论：本研究发现基于超声心动图斑点追踪技术的心脏应变分析对心脏功能障碍的早期诊断比传统超声心动图更为敏感，而且可以用于区分病理性与生理性心肌肥厚。
作者：安祥博；张幼怡；宋峣 刊期： 2016年第08期
AIM:NLRP3 inflammasome was identified as the cellular machinery responsible for activation of inflammatory processes .The present study investigated whether the activation of NLRP 3 inflammasomes contributes to hyperhomocysteinemia ( HHcy)-induced in-flammation and atherosclerosis .METHODS:ApoE-/-mice were fed regular diet , high fat ( HF) diet or HF plus high methionine (HM) diet for 10 weeks.NLRP3 shRNA or scramble shRNA viral suspension was injected twice at the 2nd and the 6th weeks after HFHM treatment.The whole aortas and aortic root sections were stained with Oil Red O for atherosclerotic lesion .Plasma lipids, ho-mocysteine ( Hcy) , IL-1βand IL-18 levels were measured .We also examined the effect of Hcy on NLRP 3 inflammasomes activation in THP-1 differentiated macrophages in the presence or absence of NLRP 3 siRNA, caspase-1 inhibitor Z-WEHD-FMK, or antioxidant N-acetyl-L-cysteine ( NAC) .RESULTS:HFHM treatment induced HHcy in ApoE-/-mice.Increased plasma levels of IL-1βand IL-18, aggravated macrophage infiltration into atherosclerotic lesion , and accelerated development of atherosclerosis were detected in HHcy mice, which were associated with the activation of NLRP 3 inflammasomes.Silencing the NLRP3 gene significantly suppressed NLRP3 inflammasomes activation , reduced plasma levels of proinflammatory cytokines , attenuated macrophage infiltration , and improved HHcy-induced atherosclerosis .Moreover, we found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1βand IL-18 in macrophages, which were blocked by NLRP3 gene silencing, Z-WEHD-FMK, or NAC.CONCLUSION:These data suggest that the activation of NLRP 3 inflammasomes contributes to HHcy-induced inflammation and atherosclerosis .Hcy activates NLRP3 inflammasomes in reactive oxygen species dependent pathway in macrophages .
作者： 刊期： 2016年第08期
目的：观察中电导钙激活钾离子通道（intermediate－conductance Ca2＋－activated K ＋channel， KCa3．1）在软脂酸（palmitic acid， PA）诱导的单核细胞跨内皮迁移中的作用及其调控机制。方法：分离2型糖尿病（type 2 diabetes mellitus， T2DM）患者外周血单核细胞（peripheral blood mononuclear cells ， PBMCs）并培养人单核细胞株（THP－1 cells），以PA刺激，通过Western blotting、RT－PCR、ELISA及细胞迁移实验观察PA对PBMCs及THP－1细胞跨内皮迁移的影响及其与KCa3．1的关系、KCa3．1与MCP－1之间的关系并探讨其信号转导通路。结果：100μmol／L PA上调体重指数（body mass index， BMI）位于20～27．9 kg／m2的T2DM患者PBMCs KCa3．1的表达并促进其跨内皮迁移，对BMI≥28 kg／m2的T2DM患者PBMCs无影响；KCa3．1特异性阻滞剂TRAM－34、NF－κB阻滞剂PDTC（100μmol／L）和Bay11－7082（10μmol／L）抑制PA诱导的BMI位于20～27．9 kg／m2的T2DM患者PBMCs跨内皮迁移；TRAM－34和KCa3．1特异性siRNA显著减少PA（200μmol／L）诱导的THP－1细胞跨内皮迁移及THP－1细胞中MCP－1的分泌和表达，anti－TLR2／4（4 mg／L）、p38MAPK抑制剂SB203580（10μmol／L）及 SB202190（10μmol／L）、PDTC（100μmol／L）和Bay11－7082（10μmol／L）显著减少PA诱导的THP－1细胞中KCa 3．1和MCP－1的表达。结论：PA通过TLR2／4－p38MAPK－NF－κB通路上调KCa3．1促进MCP－1的表达，进而诱导单核细胞的跨内皮迁移。
作者：马晓真；赵丽梅；庞正达；邓秀玲 刊期： 2016年第08期
AIM:To investigate whether KCNE 2 participates in the development of pathological hypertrophy .METHODS:Bidirectional ma-nipulations of KCNE2 expression were performed by adenoviral overexpression of KCNE 2 or knockdown of KCNE2 with RNA interfer-ence in PE-induced neonatal rat ventricular myocytes .Then overexpression of KCNE 2 in mouse model of left ventricular hypertrophy in-duced by transverse aortic constriction (TAC) by ultrasound microbubble-mediated gene transfer were used to detect the therapeutic function of KCNE2 in the development of hypertrophy .RESULTS:KCNE2 expression was significantly decreased in PE-induced hy-pertrophic cardiomyocytes and in hypertrophic hearts produced by TAC .Knockdown of KCNE2 in cardiomyocytes reproduced hypertro-phy, whereas overexpression of KCNE2 attenuated PE-induced cardiomyocyte hypertrophy .Knockdown of KCNE2 increased calcineurin activity and nuclear NFAT protein level , and pretreatment with nifedipine or FK 506 attenuated decreased KCNE 2-induced cardiomyo-cyte hypertrophy .Overexpression of KCNE 2 in heart by ultrasound microbubble-mediated gene transfer suppressed the development of hypertrophy and activation of calcineurin-NFAT and MAPK pathways in TAC mice .CONCLUSION:These findings demonstrate that cardiac KCNE2 expression is decreased and contributes to the development of hypertrophy via activation of calcineurin -NFAT andMAPK pathways .
作者： 刊期： 2016年第08期
线粒体作为细胞能量代谢的重要场所，通过氧化磷酸化过程生成ATP为细胞供能。近年的研究表明，线粒体除具有能量生成功能之外，还参与母性遗传、多种生物大分子代谢以及细胞程序性死亡等病理过程。由此可见，线粒体的自身内源性平衡直接决定细胞的命运，线粒体的生成和自噬保持动态平衡。神经元主要以氧化磷酸化提供能量，维持神经元内各种生物学功能的完整，因此神经元内线粒体总体积分数约占细胞体积的30％。脑组织缺血再灌注将导致神经元线粒体结构破坏，线粒体DNA数量减少，生成能力降低，终引起线粒体氧化磷酸化功能下降，导致神经元能量匮乏而凋亡。
作者：王来；祝世功 刊期： 2016年第08期
AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .
作者： 刊期： 2016年第08期
目的：探讨梅花鹿二杠茸和三岔茸水提物对顺铂（ CDDP）所致小鼠肾损伤的影响。方法：采用灌胃给药方式，用顺铂（15 mg／kg）诱导小鼠肾损伤模型，测定小鼠肾脏指数（KI）、血清肌酐（SCr）、血尿素氮（BUN）、肾脏组织中超氧化物歧化酶（ SOD）和谷胱甘肽过氧化物酶（ GSH－Px）活性及丙二醛（ MDA）含量，并对肾脏组织进行HE染色，观察肾脏病理学变化，研究梅花鹿二杠茸和三岔茸的水提物各剂量对小鼠肾损伤的影响。结果：与顺铂组相比，各剂量鹿茸水提物可显著降低CDDP诱导肾损伤小鼠SCr、BUN水平及肾脏MDA含量，提高SOD和GSH－Px的活性（ P＜0．05）；明显改善肾组织病理学形态，减轻CDDP对肾小管上皮细胞的损伤程度，且同等浓度下，与三岔茸相比，二杠茸水提物能更好地改善肾功能及减轻病理损伤。结论：鹿茸水提物减轻顺铂引起的小鼠肾损伤，其作用机制可能与鹿茸水提物增强小鼠肾脏组织的抗氧化能力有关。
作者：董思敏；王海璐；王全凯；张晶 刊期： 2016年第08期
目的：探讨钙敏感受体（calcium－sensing receptor，CaSR）在氧化型低密度脂蛋白（oxidized low－density lipoprotein，oxLDL）诱导的大鼠胸主动脉平滑肌细胞（A7r5细胞）增殖及迁移中的作用及信号机制。方法：BrdU掺入法检测细胞增殖；伤口愈合实验及Transwell迁移分析检测细胞迁移情况；Western blot方法检测CaSR、PCNA、ERK MAPK通路及PI3K／AKT通路的蛋白表达。结果：（1）小剂量（10 mg／L）oxLDL 作用A7r5细胞24 h促进细胞的增殖和迁移；（2）oxLDL增加A7r5细胞的CaSR表达；（3）CaSR 拮抗剂NPS2390抑制了oxLDL 的作用，而激动剂GdCl3进一步增强了oxLDL 的作用；（4）oxLDL 可促进p－AKT、p－ERK蛋白表达；（5）PI3K／AKT通路抑制剂LY294002、ERK MAPK通路抑制剂PD98059能够抑制oxLDL 诱导的细胞增殖和迁移效应；（6）NPS2390抑制了oxLDL诱导的p－AKT和p－ERK蛋白表达，而GdCl3作用相反。结论：（1）oxLDL诱导A7r5细胞增殖及迁移效应；（2）CaSR参与oxLDL诱导的A7r5细胞增殖及迁移作用；（3）CaSR 通过活化PI3K／AKT通路及ERK MAPK 信号通路参与oxLDL诱导的A7r5细胞增殖及迁移作用。
作者：李忠；徐长庆；田野；郝丽荣；李宏霞 刊期： 2016年第08期
Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine .In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia /reperfusion injury based on the reports pub-lished between January 2000 and September 2015 and indexed in the PubMed and Web of Science databases .The effect of exosomes on heart function was evaluated according to the following parameters:the area at risk as a percentage of the left ventricle , infarct size as a percentage of the area at risk , infarct size as a percentage of the left ventricle , left ventricular ejection fraction , left ventricular frac-tion shortening , end-diastolic volume , and end-systolic volume .Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function .However , further mechanis-tic studies, therapeutic safety and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury .
作者： 刊期： 2016年第08期
目的：比较柠檬酸镁与乳糖用于建立SD大鼠慢性渗透性腹泻模型的可行性和实验适用性，为大鼠慢性渗透性腹泻模型的建立提供方法学基础。方法：5周龄SPF级SD大鼠31只，随机分为正常对照（ Con ）组、柠檬酸镁腹泻（ Mg）组以及乳糖腹泻（ Lac）组。 Lac组用高乳糖饲料喂养，自由饮水；Mg组用基础饲料喂养，自由饮用柠檬酸镁溶液（镁离子浓度为4．77 g／L），不另外给予普通饮用水；Con组用基础饲料喂养，自由饮水。每天观测大鼠的一般情况和腹泻情况，腹泻14 d后测试肌力和自主活动度。随后处死全部大鼠，取结肠中段检测肠黏膜跨肠上皮电阻；取小肠下段和结肠中段，HE染色观察肠黏膜病理学变化。结果：两腹泻组大鼠均出现体重增长缓慢、毛发稀疏无光泽、乏力、活动减少等临床表现，腹泻率和腹泻指数均显著高于Con组（ P＜0．05）；Lac组腹泻指数明显高于Mg组（P＜0．05），但Mg组小肠黏膜破坏程度较Lac组稍严重。结论：两种腹泻模型均能达到慢性腹泻的要求，但存在各自的优势，需根据实验需求选择恰当的模型。
作者：刘舒；高媛；肖露；杨亭；李廷玉；陈洁 刊期： 2016年第08期
AIM:To investigate the effect of miR-214 on cardiomyocyte hypertrophy and the expression of the potential target genes . METHODS:A cell model of hypertrophy was established based on angiotensin-Ⅱ( Ang-Ⅱ)-induced neonatal mouse ventricular car-diomyocytes (NMVCs).Dual luciferase reporter assay was performed to verify the interaction between miR-214 and the 3’ UTR of MEF2C.The expression of MEF2C and hypertrophy-related genes at mRNA and protein levels was determined by RT-qPCR and Wes-tern blotting, respectively.RESULTS:The expression of ANP, ACTA1,β-MHC and miR-214 was markedly increased in Ang-Ⅱ-in-duced hypertrophic cardiomyocytes .Dual luciferase reporter assay revealed that miR-214 interacted with the 3’ UTR of MEF2C, and miR-214 was verified to inhibit MEF2C expression at the transcriptional level .The protein expression of MEF2C was markedly in-creased in the hypertrophic cardiomyocytes .Moreover, miR-214 mimic, in parallel to MEF2C siRNA, inhibited the expression of hy-pertrophy-related genes in Ang-Ⅱ-induced NMVCs.CONCLUSION:MEF2C is a target gene of miR-214, which mediates the effect of miR-214 on attenuating cardiomyocyte hypertrophy .
作者： 刊期： 2016年第08期
目的：PKG在血管硝酸甘油（nitroglycerin， NTG）耐受形成中起重要作用，PI3K／Akt信号通路与血管张力调节关系密切，本研究旨在探讨该通路在NTG耐受形成中的作用及其机制。方法：通过猪离体冠状动脉孵育NTG（10－5 mol／L，24 h）建立离体NTG耐受模型；通过皮下注射NTG（20 mg／kg体重，每天3次，连续3 d）建立小鼠在体NTG耐受模型；运用离体血管环灌流、Western blot、实时定量PCR及免疫荧光等方法进行研究。结果：离体和在体研究表明，耐受组血管对硝酸甘油的舒张反应较对照组显著减弱，并且耐受组血管的p－Akt （Ser473）蛋白水平显著增加。 PI3K的特异阻断剂LY294002与NTG共孵育冠状动脉24 h，可显著抑制耐受组引起的p－Akt （Ser473）蛋白水平升高，同时部分改善了血管对NTG的反应性。耐受组冠状动脉PKG的蛋白和mRNA水平较对照组明显降低，且均可被LY294002所反转。耐受组血管的p－FoxO1（ Ser256）蛋白水平较对照组显著升高，且出现由胞核向胞浆的转位，以上现象均可被LY294002所阻断。结论：活化的PI3K／Akt通过促进FoxO1的出核，抑制了PKG的表达，从而导致NTG耐受。
作者：安苑铭；李妍静；张城林；丛馨；吴立玲；窦豆 刊期： 2016年第08期
目的：建立大鼠心肌缺血再灌注损伤模型和氧化应激损伤细胞模型，研究抗肌萎缩蛋白Dp71在损伤心肌及细胞中的表达，探讨其拮抗心肌细胞凋亡的作用及其分子机制。方法：阻断SD大鼠冠状动脉左前降支血流30 min后恢复血流复制心肌缺血再灌注损伤模型，观察心肌形态学、LDH变化及心肌细胞凋亡；检测再灌注不同时间心脏Dp71蛋白和mRNA表达。建立H9c2细胞氧化应激损伤模型，检测H2 O2刺激后细胞中Dp71蛋白和mRNA的表达。 H9c2细胞转染Dp71过表达质粒，流式细胞术检测Dp71高表达对H2 O2诱导H9c2细胞凋亡率的影响。 Western blot检测过表达Dp71对细胞中lamin B1和Bcl－2蛋白表达的影响；对H2 O2刺激下lamin B1和Bcl2蛋白表达改变的影响。结果：与假手术组相比，再灌注损伤组HE染色心肌出现明显形态改变，LDH明显增加， IR组心肌细胞凋亡数显著增加。 IR后各时点Dp71 mRNA和蛋白表达水平均增加（ P＜0．05）。0．2 mmol／L H2 O2刺激细胞16 h Dp71蛋白及mRNA表达明显升高（ P＜0．05）。 H9c2细胞中转染Dp71过表达质粒可抑制H2 O2所诱导的细胞凋亡；H9c2细胞中过表达Dp71引起lamin B1和Bcl2表达增高，高表达的Dp71可以抑制过氧化氢刺激引起的lamin B1和Bcl2表达下降。结论：Dp71 mRNA和蛋白表达在大鼠心肌缺血再灌注损伤模型和H2 O2诱导H9c2氧化应激损伤模型中明显升高。 H9c2细胞过表达Dp71通过提高Bcl2和lamin B1表达而抑制H2 O2诱导的细胞凋亡。
作者：赵帅；邹江；刘梅冬；陈广文；王浩；余凤秀；肖献忠；谭斯品 刊期： 2016年第08期
目的：房室传导阻滞是心脏电激动传导过程中，发生在心房和心室之间的电激动传导异常，可导致心律失常。前期，我们发现一个遗传性房室传导阻滞伴肥厚型心肌病家系，本次工作主要对其致病基因及机制进行研究。方法：采用候选基因测序的方法对已经确诊为房室传导阻滞的心脏病患者进行致病基因分析，对报道与心脏病相关的 TRP4、 SCN5A、 SCN1B、NKFX2．5、CLCA2和LMNA共6个基因测序并确定致病基因；构建致病基因的野生型和突变型质粒；克隆野生型和突变型，激光共聚焦显微镜检测野生和突变型蛋白在细胞定位，利用Western blot检测目的蛋白的表达情况对该突变功能进行分析。结果：遗传学分析显示在家系中患者LMNA基因第10号外显子缺失，并与疾病共分离。 Western blot结果显示突变型lamin蛋白表达水平正常，定位结果显示，野生型蛋白位于细胞核核膜，而突变型蛋白在核膜上和核内均有表达。 LMNA异常可引起房室结细胞死亡与纤维化，导致房室传导速率降低，并发生房室传导阻滞。自噬和凋亡是细胞死亡的重要形式，LC3－II是检测自噬的标志蛋白。应用Western blot检测LC3－II，结果显示LMNA突变不影响该蛋白表达。结论：本次研究中，我们发现了一个新的导致遗传性房室传导阻滞伴肥厚型心肌病的LMNA基因突变，该突变可使其编码的蛋白不能正确定位于细胞核膜，导致细胞核核纤层结构异常。核纤层在细胞分裂中呈现周期性的变化，因此核纤层的异常会对细胞正常周期产生重要影响从而导致细胞的异常死亡。这可能是导致该家族成员发生房室传导阻滞的原因。
作者：曹祝兵；李思思；臧小彪；凃欣 刊期： 2016年第08期
AIM:Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines .Inter-leukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure.Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) gene contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it .METHODS AND RESULTS:A total of 1713 adults patients with congestive heart failure and 1713 age-and sex-matched controls were genotyped for promoter SNPs, rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure .Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (P<0.01) after adjustment for multiple cardiovascular risk factors including age , sex, smoking status, diabetes, hypertension and dyslipidemia.This association was evident in both ischemic and non-ischemic heart failure (P<0.05).Furthermore, prospective fol-low-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs 4819554 in IL17RA was significantly associated with cardiovascular mortality (P<0.05) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.CONCLUSION:This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of conges-tive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure.These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure path -ogenesis and progression .
作者： 刊期： 2016年第08期
AIM:To investigate the regulation mechanism for insufficient KChIP 2 expression induces Ito,f downregulation and arrhythmogene-sis in cardiac hypertrophy .METHODS:Bidirectional manipulations of MG 53 expression were performed by adenoviral overexpression of MG53 or knockdown of MG53 with RNA interference in neonatal rat ventricular myocytes with or without PE stimulation .Ito,f was re-corded with patch clamp in whole-cell mode 48 h after adenoviral transfection .Then the WT or MG53 knockout ( MG53 -/-) mouse model of left ventricular hypertrophy induced by transverse aortic constriction ( TAC) were used to detect the susceptibility to ventricu-lar arrhythmia.RESULTS: Here, we show muscle-specific MG53 regulates KChIP2 expression and Ito,f densities, where they are downregulated in hearts from MG53 knockout mice and MG53 knockdown rat cardiomyocytes , but upregulated in MG53 overexpressed cells.MG53 expression is decreased in phenylephrine ( PE)-induced cardiomyocyte hypertrophy and restoration of MG 53 rescues PE-induced downregulation of KChIP2 and Ito,f.Furthermore, MG53 is decreased in a mouse model of hypertrophy induced by transverse aortic constriction and ablation of MG 53 increases the susceptibility to ventricular arrhythmia by exaggerating Ito,f remodeling.CON-CLUSION:These findings establish MG53 as a novel regulator of Ito,f and its central role in arrhythmogenesis in hypertrophy .
作者： 刊期： 2016年第08期
AIM:MicroRNAs ( miRNAs) were recognized to play significant roles in cardiac hypertrophy .But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy .This study investigates the potential roles of microRNA-1 (miR-1) and microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy .METHODS:An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC).In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte .RESULTS:miR-1 and-16 expression were markedly de-creased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats .Overexpression of miR-1 and -16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes .Expression of cyclins D1, D2 and E1, CDK6 and phosphorylated pRb was increased in hypertrophic myocardium and hypertrophic cardiomyocytes , but could be reversed by enforced expression of miR-1 and -16.CDK6 was validated to be modulated post-transcriptionally by miR-1, and cyclins D1, D2 and E1 were further validated to be modulated post-transcriptionally by miR-16.CONCLUSION: Attenuations of miR-1 and -16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2, E1 and CDK6, and activating cyclin/Rb pathway.
作者： 刊期： 2016年第08期
目的：探讨高盐饮食对Dahl盐敏感大鼠肾小管上皮向间质转化（ EMT ）和肾脏纤维化的影响。方法：7～8周龄雄性Dahl盐敏感大鼠（SS， n＝24）及SS－13BN大鼠（13BN， n＝12），高盐、正常饮食干预4周与8周，测血压及血尿生化指标；用Masson染色评估肾脏纤维化程度；免疫组化和实时定量PCR检测肾小管上皮标志E－cadherin和间质细胞标志α－SMA mRNA和蛋白的表达情况。结果：（1）相较基线期，SS和13BN大鼠干预后收缩压增高，SS大鼠增高幅度更为明显；8周高盐干预时血压显著高于4周（P＜0．01）。（2）4周高盐负荷后，2种大鼠肾脏均出现胶原纤维沉积，且SS高盐组多于13BN高盐组。8周时， SS高盐组肾小球和间质胶原沉积较4周进一步加重。（3）4周和8周高盐干预后，与SS正常饮食组相比，SS高盐组肾脏E－cadherin表达显著减少，α－SMA 表达明显增加。（4）肾脏纤维化程度与与肾小管EMT 的发生显著相关（ E－cadherin： r ＝－0．787；α－SMA：r＝0．866）。结论：高盐饮食可诱导Dahl盐敏感大鼠肾小管上皮细胞EMT的发生，促进肾脏纤维化。
作者：汪洋；牟建军；褚超；吕永波 刊期： 2016年第08期
中国病理生理杂志
主管:中国科学技术协会
主办：中国病理生理学会
