| AIM To seek secure and efficacious anti-ischemia/reperfusion (I/R) injury drugs from the copretreatment of our abundant herbal resources and isosorbide mononitrate. On the basis of the Chinese herbal compound capsule "ShuMai capsule" and isosorbide mononitrate all having obviously clinic effects on ischemic heart diseases, this subject is administrated to study the effects of the copretreatment of the two drugs in protection of myocardial ischemic reperfusion injuries in simulating ischemic preconditioning (IPC) and its action mechanism on myocardial I/R injury in rats from functional, biochemical, morphological and molecular level.METHOD 108 Wistar rats were divided into 9 groups of 12 rats each: sham-operation group(SIR,NS 5ml/kg);ischemic-reperfusion group(IR, NS 5ml/kg);Ischemic preconditioning group(IPC,NS 5ml/kg); ShuMai capsule group (SM,100mg/kg/d);ShuMai plus glibencalmide capsule group(SM,100mg/kg/d+GLI,0.3g/kg); Isosorbide-mnonitrate group (IM, 10mg/kg/d ) ;Isosorbide-mnonitrate plus glibencalmide (IM,10mg/kg/d+GLI, 0.3g/kg);ShuMai plus Isosorbide-mnonitrate group (SM,50mg/kg/d+IM,,5mg/kg/d) ;ShuMai plus Isosorbide mnonitrate plus glibencalmide(SM,50mg/kg/d+IM,5mg/kg/d +GLI,0.3g/kg).Based on the classical rat model of ischemic preconditioning by the coronary artery ligation, ischemic preconditioning mode was cultured by ischemic for five minutes,reperfusion for five minutes,then repeating three times,while the simple ischemic model was ischemic for 30minutes and reperfusion for 2hours,all rats were subjected to ischemic for 30min and reperfusion for 2hrs.ShuMai and Isosorbide-mnonitrate were given 7 days brfore the test, glibencalmide were injected 30 minutes before the last therapy drug given. The myocardial infarction size (MIS) was determined by nitro-blue tetrazoluim stain, indicated by the ratio of non-stained size and area of all myocardium slices. Electrocardiograms of lead II were recorded at five time points: before operation, 15min after ischemic, reperfusion instant, and 30min, lhr, 2hrs after reperfusion respectively.The changes of ST segment elevation and T wave amplitude were determined. The occurrence of pathological Q wave was counted. SOD MDA CK NO CGRP 6-Keto-PGF1 in the blood were determined.Using the immuno-histochemical staining and RT-PCR methods,the expression of PKC and its mRNA are observed.T-test and Fisher's exact test were used for the statistical analysis.RESULTS (l)MIS: In the IPC and therapy groups, the ratios of the infarct size of the area at risk (lS/ARR)were significantly lower than IR group (40.20%±5.02%) which were respectively: 16.67%±2.15% 20.05%±3.44% 26.28%±2.10% 30.19%±3.46%, P<0.01,while in GLI corresponding contrast groups, MIS were respectively significantly increased: 39.06%±4.80% 40.47%±4.14% 40.92%±2.92%, P<0.01. (2)Electrocardiogram:In the IPC and therapy groups,the changes of ST segment elevation and T wave amplitude were attenuatedsignificantly,while in GLI corresponding contrast groups,the changes of ST segment and T wave were highly elevated P<0.05, and the occurrence frequency of pathological Q wave was significantly multiplied P<0. 05. (3)Blood biochemical indexes: Compare to IR group,the concentrations of SOD NO CGRP 6-Keto-PGF1 in IPC and therapy groups were significantly increased and the concentrations of MDA CK were significantly decreased;while in GLI corresponding contrast groups, the level of SOD MDA . CK and NO are significantly different compared with therapy groups, and other biochemical indexes had significant differences compared to SM group.(4)PKC:Using the immunohistochemical staining and RT-PCR methods,we can see that the expression of PKC protein and PKC-mRNA in IPC and therapy groups are significantly increased . CONCLUSION: ShuMai capsule and isosorbide mononitrale mimic the effects of the ischemic preconditioning on myocardial ischemic reperfusion injury which are partly abolished by glibenclamide, a kind of ATP sensitive potassium channel blocker.The cardioprotective effects of ShuMai and isosorbide mononitrate capsule are mediated by protein kinase C linked mechanism in rat hearts.
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