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SB203580对肾缺血/再灌注损伤时细胞凋亡及p38MAPK影响的实验研究 被引量:16

Experimental study on the influence of SB203580 on cell apoptosis and p38MAPK in renal ischemic/reperfusion injury
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摘要 目的 探讨不同时间及不同浓度p38MAPK特异性抑制剂SB2 0 35 80对肾缺血 /再灌注损伤过程中肾功能、细胞凋亡及 p38MAPK活性、表达量、p38MAPK底物的影响。 方法  4 9只大鼠按缺血 /再灌注及给药时间的不同 ,随机分为 7组 ,每组7只大鼠按正交拉丁方表的顺序 ,经尾静脉注射相同体积、不同剂量的SB ,使其在大鼠体内达到不同的浓度。测定BUN和Scr;用TUNEL试剂盒检测细胞凋亡情况 ;Westernblot技术用于蛋白定性及半定量分析。结果 SB可显著减轻大鼠肾缺血 /再灌注损伤造成的Scr和BUN的升高、肾小管上皮细胞的凋亡及 p38MAPK的激活 ,但存在模型、剂量及给药时机的差异 (P<0 .0 5 ) ,缺血前 3h之前给药 ,使其体内血药浓度达到 5 μmol/L左右可取得较好的效果。 结论 SB可显著减轻大鼠肾缺血 /再灌注损伤 ,在缺血前 3h之前给药 ,同时使其血药浓度达到 5 μmol/L左右可取得最佳效果。 Objective To explore the influence of p38MAPK peculiar inhibitor SB203580, at different time and with different concentration, on renal function, apoptosis, p38MAPK activity, express quantity and p38MAPK substrate in the course of renal ischemic/reperfusion injury. Methods Forty-nine rats were randomly divided into 7 groups and each group 7 rats according to the different time of ischemic/reperfusion injury and medication. Based on the orthogonal square Latin table, identical milliliter number but different dosages of SB, were injected, in caudal vein, reaching different density in the rat body. BUN , Scr and apoptosis were detected. The qualitative and half quantitative analyses for protein were done by Western blot. Results SB could significantly alleviate rat renal ischemic/reperfusion injury, decrease BUN, Scr, renal tubular epithelial apoptosis and the activation of p38MAPK. But there was the difference of model, dosage and medication occasion(P<0.05). A better effect could be acquired if 5 μmol/L of SB was injected 3 h before renalischemia. Conclusion SB can alleviate rat renal ischemic/reperfusion injury conspicuously if injection of SB before 3 h ischemia, and making blood medicine cncentration to be about 5 μmol/L.
出处 《山西医科大学学报》 CAS 2004年第4期317-321,共5页 Journal of Shanxi Medical University
基金 山西省自然科学基金资助项目 ( 2 0 0 0 10 72 )
关键词 再灌注损伤 SB203580 P38MAP激酶 细胞凋亡 大鼠 reperfusion injury SB203580 kidney p38MAP kinase apoptosis rats
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