摘要
目的探究内质网应激(endoplasmic reticulum stress,ERS)是否通过影响线粒体功能,从而导致心肌重构的机制。方法选择30只8周龄雄性SD大鼠给药前随机分为对照组、衣霉素组、4-苯基丁酸(4-PBA)组,每组10只。衣霉素组腹腔注射内质网应激激动剂衣霉素;4-PBA组在注射衣霉素基础上给予灌胃内质网应激抑制剂4-PBA;对照组给予腹腔注射生理盐水。连续给药4周后,采用超声心动图检测左心室舒张早期血流峰值(E)/左心室舒张晚期血流峰值(A),检测大鼠心肌组织增强子结合蛋白环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)、线粒体融合蛋白2(MFN2)、转化生长因子β_1(transforming growth factor-β_1,TGF-β_1),计算胶原容积分数。结果衣霉素组胶原容积分数、CHOP以及TGB-β1表达明显高于对照组和4-PBA组(P<0.05,P<0.01),E/A明显低于对照组和4-PBA组(0.67±0.11 vs 1.12±0.06和1.03±0.05),且MFN2明显低于对照组(0.19±0.09vs 1.44±0.41),差异有统计学意义(P<0.05)。结论 ERS影响其交联细胞器-线粒体的功能,可能是其致心肌结构重构的机制之一。
Objective To study whether endoplasmic reticulum stress(ERS)can lead to myocardial structure remodeling by affecting mitochondrial function.Methods Thirty SD male rats aged 8 weeks were randomly divided into control group(n=10),tunicamycin(TN)treatment group(n=10),and 4-PBA treatment group(n=10).Four weeks after the rats in TN group and 4-PBA group received intraperitoneal injection of TN,those in 4-PBA recived intraperitoneal injection of TN followed by intragastric 4-PBA,and those in control group receiced intraperitoneal injection of normal saline,their left ventricular early flow rate(E)and late flow rate(A)were measured by echocardiography.Expressions of CHOP,MFN2 and TGF-β1 in myocardial tssue were detected.Collagen volume fraction(CVF)was calulated.Results The CVF and expression levels of CHOP and TGB-β1 were significantly higher while the E and A were significantly slower and the expression level of MFN2 was significantly lower in TN group than in control group(P<0.05).The CVF and expression levels of CHOP and TGB-β1 were significantly lower while the E and A were significantly faster in 4-PBA group than in TN group(P<0.05).Conclusion Effect of ERS on mitochondrial function of its organedle is one of the mechanisms underlying myocardial structure remodeling.
引文
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