新肾素血管紧张素系统通路与脑心综合征关系的实验研究
Research on the relationship between the new RAS and cerebro-cardial syndrome
目的 :研究新肾素血管紧素(rennin angiotension system,RAS)系统通路在脑心综合征发生发展中的作用,探讨脑心综合征的发病机制。方法 :健康Wistar大鼠(250g±30g)随机分为空白对照组,模型对照组,氯沙坦组,氯沙坦+A779(angiotension1-7 specificity receptor blocker, A779)组。每组内再分为4小时组,24小时组,每组8只。腹腔注射水合氯醛0.3g/kg麻醉大鼠,线栓法阻塞大脑中动脉制作局造型脑缺血模型,同时监测各组大鼠心电图。模型对照组术前30分钟灌胃给予等容量的蒸馏水,氯沙坦组以及氯沙坦+A779组术前30分钟灌胃给予氯沙坦(10mg/kg),氯沙坦+A779组在栓线入大脑中动脉时腹腔注射A779(120ng/kg)。而后在规定的各时间点颈总动脉取血离心取血浆置于-80℃待测。取左室前壁心肌组织分为两份分别于多聚甲醛和-80℃保存,再取脑制作脑片,利用氯化三苯基四氮(2,3,5-triphenyltetrazolium chlorid,TTC)染色确定模型是否成功,并测量模型对照组不同时间点梗塞率的变化。用化学发光法检测组织和血浆中血管紧张素Ⅱ(angiotensionⅡ,AngⅡ)的含量,用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)法检测组织和血浆中血管紧张素1-7(angiotension1-7,Ang-(1-7))的含量。用苏木素伊红染色(hematoxylin and eosin stain,HE)观察各组大鼠心肌损伤程度,用免疫组化检测心肌AngⅡ,Ang-(1-7)的表达。结果 :模型对照组心肌损伤严重,氯沙坦组心肌损伤有所减轻。氯沙坦+A779组心肌损伤较氯沙坦组较重。心肌损伤程度随着时间的延长相应加重。模型对照组血浆中AngⅡ的含量相比空白对照组增加(P<0.01),氯沙坦组AngⅡ的含量相比模型对照组显著增加(P<0.01),氯沙坦+A779组AngⅡ的含量与氯沙坦组相比显著降低(P<0.01)。模型对照组血浆中Ang-(1-7)的含量相比空白对照组显著降低(P<0.01),氯沙坦组Ang-(1-7)的含量相比模型对照组升高(P<0.01),氯沙坦+A779组Ang-(1-7)的含量相比氯沙坦组降低(P<0.01)。血浆AngⅡ、Ang-(1-7)的含量分别随着时间的延长相应增加(P<0.01)。心肌局部AngⅡ、Ang-(1-7)的含量变化趋势分别与血浆中AngⅡ、Ang-(1-7)含量的变化趋势一致。结论 : Ang-(1-7)通过Ang-(1-7)特异性受体(D-Ala-7-Ang-(1-7),Mas)参与脑心综合征的发生发展,并对脑梗所致的心肌损伤起到保护作用。
Objecitve: To invesgate the role of the new RAS in the development of Cerebro-cardial syndrome. To invesgate the pathogenesis of the Cerebro-cardial syndrome.Methods: The healthy Wistar rats (250±30g) were devided into four groups randomly: the blank control group, the model group, the losartan group, the losartan+A779 group.Each group was devided into two subgroup: 4 hour and 24 hour(n=8). The rats were intraperitoneally injected with hydral 0.3g/kg, The cerebral ischemia model was induced by processed thread inside the right middle cerebral artery,the ECG was moniterd simutaniously. The model group was intragastrically given distilled water with equal volume 30 minutes before the experiments. The losartan group was intragastrically given losartan (10mg/kg) 30 minutes before the experiments, as well as the losartan+A779 group. A779 was intraperitoneally given (120ng/kg)as soon as the processed thread inside the middle cerebral artery in The losartan+A779 group. Acquire the blood from carotid artery, then centrifugate the blood to get the plasma which was stored at --80℃.Anterior left ventricular wall myocardial tissue was divided into two slips, one was fixed with paraform, the other was stored at -80℃. The cerebral slices were stained with TTC to clarify the success of model creation, and the infarct rate was inspected in each model group. The content of AngⅡin the myocardial tissue and the plasma was detected by chemical luminescence.The content of Ang-(1-7) in the myocardial tissue and the plasma was detected by ELISA. The extent of myocardial damage was detected by HE. The expression of Ang-(1-7) and AngⅡof myocardial tissue was detected by immunohistochemistry.Result: The model group showed severe myocardial injury. In losartan group, myocardial injury is reduced. Myocardial jury in losartan + A779 group was heavier than that of the losartan group. HE results of each 24 hour group of myocardial was heavier than that of each 4 hour group. Compared with the blank control group, the content of Ang II in plasma of the model group was rised(P <0.01). Compared with the model group, Ang II of the lostarn group was rised(P <0.01). Ang II of lostarn+A779 group was lower than that of lostarn group(P <0.01). Compared with the blank control group, the content of Ang-(1-7) in plasma of the model group was decreased(P <0.01); Ang-(1-7) of lostarn group was higher than that of the model control group (P <0.01); Ang-(1-7) of lostarn+A779 group was lower than that of the model group and the lostarn group(P <0.01).The content of Ang II and Ang-(1-7) of each 24 hour group in plasma was respectively rised accordingly with the extension of time(P <0.01). The changes of Ang II and Ang-(1-7) of each group in myocardial tissue were consistent with that of plasma.Conclusion: Ang-(1-7) gets involved in the development of cerebro-cardial syndrome by mas receptor, and plays a role in protection of the myocardial injury induced by cerebral infraction.
赵剑、王娜、王玲、夏青
基础医学内科学神经病学、精神病学
新肾素血管紧素系统通路脑心综合征ngⅡng-(1-7)779
he new RASerebro-cardial syndromengⅡng-(1-7)779
赵剑,王娜,王玲,夏青.新肾素血管紧张素系统通路与脑心综合征关系的实验研究[EB/OL].(2012-06-05)[2025-08-23].http://www.paper.edu.cn/releasepaper/content/201206-76.点此复制
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