青藤碱对心脏移植大鼠急性排斥反应及环氧化酶2活性的影响

目的研究环氧化酶2(COX-2)抑制剂青藤碱在大鼠急性心脏移植物排斥反应模型中的作用。方法进行40次SD→W istar的大鼠腹部心脏移植,移植后大鼠随机分为实验组(20只)和对照组(20只),实验组大鼠给予青藤碱30 mg.kg-1.d-1,对照组给予生理盐水,评价生存时间,检测移植心切片,进行排斥反应的病理分析和评价COX-2活性。结果实验组移植物生存时间12.5 d±2.6 d明显高于对照组生存时间6.8 d±0.5 d(P=0.001),移植后3 d、5 d时,实验组的炎性反应、血管内膜炎症、心肌水肿心肌坏死明显减轻。移植心的细胞凋亡明显减少(P<0.05),移植后5 d COX-2蛋白和mRNA表达减少。结论青藤碱能够延长移植物生存时间,减轻心肌损坏和炎症反应。

Effects of the alkaloid sinomenine on COX-2 activity and acute rejection in heart allografts: an experiment with rats

OBJECTIVE: To evaluate the effects of the alkaloid sinomenine (SIN), a COX-2 inhibitor, on the acute rejection in heart allografts. METHODS: Forty Wistar rats received the allograft of the hearts of 40 SD rats into the peritoneum. Then the recipients were randomly divided into 2 groups: SIN group, injected with SIN within 24 hours after the operation; and control group, injected with normal saline. The survival time was observed. The heartbeat was examined every day. The Wistar rats were killed 3 and 5 days after the operation respectively and the left ventricular tissues were taken to undergo pathological examination to detect the acute rejection and cell apoptosis. Immunochemistry and Western blotting were used to detect the COX-2 protein, and RT-RCR was used to detect the COX-2 mRNA. The mean numbers of apoptotic cardiomyocytes were determined with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) technique. RESULTS: The survival time of the SIN group was 12.5 +/- 2.6 days, significantly longer than that of the control group (6.8 +/- 0.5 days, P = 0.001). Examination 3 and 5 days after the treatment of SIN, the extents of inflammatory reaction, endovasculites, myocardial edema, and cardiomyocyte damage in the allografts of the SIN group were all significantly less, the mean numbers of apoptotic cardiomyocyte was significantly smaller compared with the control group (all P < 0.05). At day 5, the levels of COX-2 protein and mRNA of the SIN group were both significantly lower than those of the control group. CONCLUSION: Inhibition of COX-2 prolongs the allograft survival and reduces the myocardial damage and inflammation during acute cardiac allograft rejection.