摘要
(1)目的观察替米沙坦对糖尿病心肌损害大鼠GRP78、PERK、CHOP表达的影响并探讨其机制。(2)方法将36只Wistar大鼠随机分成正常对照组(NC组)、糖尿病心肌损害组(DMD组)和替米沙坦治疗组(DMD+Telmi组)。采取高脂肪饲料喂养加一次性腹腔注射链脲佐菌素的方式制备糖尿病心肌损害大鼠模型,DMD+Telmi组大鼠给予替米沙坦干预8周。采用左室插管评估大鼠心功能;HE染色光镜下观察大鼠心肌组织病理形态学改变;Western blot检测大鼠心肌组织GRP78、PERK、CHOP蛋白表达情况;TUNEL染色法检测大鼠心肌细胞凋亡情况。(3)结果 DMD组与NC组大鼠相比左室舒张末期压(LVEDP)显著升高,左室收缩压(LVSP)和左室压力上升或下降最大速率(±dp/dt max)显著降低;DMD+Telmi组与DMD组相比左室舒张末期压(LVEDP)显著下降,左室收缩压(LVSP)和左室压力上升或下降最大速率(±dp/dtmax)显著升高。光镜下NC组大鼠心肌细胞排列整齐,形态规则;DMD组大鼠心肌细胞肥大,排列紊乱,形态不规则;DMD+Telmi组相比于DMD组病理形态有所改善。DMD相比于NC组GRP78、PERK、CHOP蛋白表达量明显升高(P<0.05);DMD+Telmi组相比于DMD组GRP78、PERK、CHOP蛋白表达量明显下降(P<0.05)。TUNEL检测DMD组大鼠相比于NC组大鼠心肌细胞凋亡数量明显增加;DMD+Telmi组大鼠相比于DMD组大鼠心肌细胞凋亡数量明显减低。(4)结论替米沙坦能减轻糖尿病大鼠的心肌病理损伤,改善心功能,并可能通过抑制内质网应激减少心肌细胞凋亡。
Objective To observe the effect of telmisartan on the expression of GRP78,PERK and CHOP in rats with diabetic myocardial damage and to explore its mechanism.Methods 36 Wistar rats were randomly divided into normal control group（group NC）,diabetic myocardial damage group（group DMD）and telmisartan treatment group（group DMD＋Telmi）.Diabetic cardiomyopathy rats were induced by high-fat diet plus intraperitoneal injection of streptozotocin.Rats in group DMD＋Telmi were given telmisartan for 8 weeks.Left ventricular cannulation was used to evaluate cardiac function in rats.HE staining was used to observe pathological changes of rat myocardium under light microscope.Western blot was used to detect the expression of GRP78,PERK and CHOP protein in rat myocardium,and TUNEL staining was used to detect cardiomyocyte apoptosis in rats.Results Compared with NC group rats,DMD group rats left ventricular end diastolic pressure（LVEDP）increased significantly,left ventricular systolic pressure（LVSP）and left ventricular pressure increase or decrease the maximum rate（±dp/dtmax）significantly decreased;compared with DMD group rats,DMD＋Telmi group rats left ventricular end diastolic pressure（LVEDP）decreased significantly,left ventricular systolic pressure（LVSP）and left ventricular pressure increase or decrease the maximum rate（±dp/dtmax）increased significantly.Under light microscope,myocardial cells in NC group were arranged orderly and regularly.In group DMD,cardiomyocytes were hypertrophic,arranged in disorder and irregular in shape.Compared with group DMD,the pathological morphology of DMD＋Telmi group was improved.Compared with group NC rats,the expression level of GRP78,PERK and CHOP in group DMD rats increased significantly（P 〈0.05）;and compared with group DMD rats,the expression of GRP78,PERK and CHOP in group DMD＋Telmi rats decreased significantly（P 〈0.05）.TUNEL detection showed that the number of cardiomyocytes apoptosis increased significantly in DMD group compared with NC group,and the number of cardiomyocytes apoptosis in DMD＋Telmi group was significantly lower than that in DMD group.Conclusion Telmisartan can alleviate myocardial pathological damage and improves cardiac function in diabetic rats,and may reduce cardiomyocyte apoptosis by inhibiting endoplasmic reticulum stress.
作者
曾招军
黄安静
远迪
董云朋
张春来
周洪霞
ZENG Zhaojun,HUANG Anjing,YUAN Di(North China University of Science and Technology, Tangshan 063000, China)
出处
《华北理工大学学报（医学版）》
2018年第4期265-269,281,共6页
Journal of North China University of Science and Technology：Health Sciences Edition
关键词
糖尿病心肌损害
内质网应激
凋亡
替米沙坦
Myocardial injury of diabetes mellitus
Endoplasmic reticulum stress
Apoptosis
Telmisartan
