【摘要】 目的: 探讨川芎嗪对缺血/再灌注(I/R)损伤大鼠肾功能、肾脏组织形态学、细胞凋亡及相关基因表达的 影响 . 方法 : 将大鼠随机分为假手术(S)组、I/R组、再灌注后给予川芎嗪(TPpst)组、再灌注前给予川芎嗪(TPpre)组,各组分别采用化学法测定血尿素氮和肌酐,光镜和电镜观察肾组织形态学变化,原位末端标记法检测肾脏细胞凋亡指数,免疫组化和免疫印迹法检测肾脏Bl2和Bax蛋白的表达. 结果: TPpre组较I/R组血尿素氮和肌肝显著降低,肾小管损伤评分减轻,分别为[(21.8±5.2)vs (31.1±4.4) l/L,P<0.01) ],[(196±55)vs (295±64)μl/L,P<0.01)],[(372±46) vs (563±62),P<0.01) ];肾小管上皮细胞损伤及超微结构改变明显减轻,肾组织凋亡细胞数明显减少[(13.6±2.9) vs (28.8±4.6),P<0.01)];Bl2蛋白表达明显增强[(1.15±0.12) vs (0.88±0.12),P<0.05)],Bax表达明显减弱[(0.87±0.11) vs (1.15±0.09),P<0.05)]. 结论: 川芎嗪可明显减轻I/R肾损伤,其保护作用机制与Bl2蛋白表达增强和Bax蛋白表达减弱介导的肾脏细胞凋亡有关.
【关键词】 川芎嗪;肾脏;再灌注损伤;细胞凋亡;保护
【Abstrat】AI: T explre Ligustrazine (Tetraethylpyrazine, TP) n the effet f in rats it rat renal funtins, renal tissue rphlgy, ell apptsis and expressins f related genes in rats ith. ETHDS: Frty istar rats f Either sex ere randly divided int 4 grups, hih ere sha peratin(n=10), I/R del(n=10), TPpst (n=10, intraperitneal TP 32 g/kg per 6 h after reperfusin fr 30 in) and TPpre (n=10, intraperitneal TP 32 g/kg at 45 in, 8, 16, 24 h befre isheia) grups. Bld urea nitrgen and reatinine ere deteted by heial ethd. Renal ell apptti index as exained by eans f terinal dexynuletidyl transferaseediated dUTP nik end labeling(TUNEL). The expressins f Bl2 and Bax in kidney as iunhistheially evaluated and quantified by estern Blt analysis. The kidney histlgy ere bserved by light and eletrn irspe. RESULTS: pared ith thse in the TPpre grup, the bld urea nitrgen[(21.8±5.2)vs (31.1±4.4) l/L,P<0.01], the reatinine [(196±55) vs (295±64)μl/L,P<0.01)] and the sre f injury in renal tubules [(372±46) vs (563±62),P<0.01) ] ere dereased signifiantly in I/R grup. The hanges f injury and ultrastruture in tubular epithelial ells ere signifiantly attenuated in TPpre grup. By Tetraethylpyrazine pretreatent, the apptti index (13.6±2.9 vs 28.8±4.6, P<0.01) and the expressin f Bax (0.87±0.11 vs 1.14±0.09, P<0.05) ere dereased signifiantly, and the expressin f Bl2(1.15±0.12 vs 0.88±0.12, P<0.05) as inreased signifiantly as pared ith that in I/R grup. NLUSIN: Tetraethylpyrazine an attenuate kidney I/R injury, and prtetive ehanis ay be partly thrugh inhibitin f ell apptsis by regulating the expressins f apptsisrelated genes Bl2 and Bax.
【Keyrds】 tetraethylpyrazine; kidney; reperfusin injury; apptsis; prtetin
0 引言
川芎嗪是从伞形科植物川芎根茎中分离提纯的一种生物碱单体,其基本化学结构为四甲基吡嗪,具有扩张血管、改善微循环等作用,临床上广泛用于心脑血管疾病的 治疗 ,并取得较好疗效. 川芎嗪对肾脏缺血/再灌注(I/R)损伤的保护作用已被大量 研究 证实[1-2],但这种保护作用的机制尚不完全清楚,我们通过观察川芎嗪对I/R损伤大鼠肾功能、肾组织形态学、细胞凋亡及Bl2和Bax蛋白表达的影响,进一步探讨川芎嗪对肾I/R损伤的保护作用机制.
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