目的 研究雌激素(estrogen,E2)对大鼠肾缺血再灌注损伤后肾叶间动脉缝隙连接蛋白43(connexin43,Cx43)表达的影响。方法 建立SD大鼠肾缺血再灌注损伤模型,随机分为正常组、假手术组、缺血再灌注损伤组和E2干预组,于缺血再灌注损伤后24h检测肾功能变化;肾组织切片HE染色行Paller评分,量化肾损害程度。运用压力肌动技术检测各组大鼠肾叶间动脉的舒缩功能。免疫荧光技术、qRT-PCR及Western-blot检测各组大鼠肾叶间动脉Cx43表达的差异。结果 E2能明显降低肾缺血再灌注损伤大鼠血清中血清肌酐(Cr)和尿素氮(BUN)水平,差异有统计学意义(P〈0.05),且能显著改善肾组织损害程度。肾缺血再灌注损伤后肾叶间动脉收缩率(24.80±3.70)%,给予E2干预后肾叶间动脉收缩率为(41.60±3.50)%,明显高于缺血再灌注损伤组,差异有统计学意义(P〈0.05)。E2干预组肾叶间动脉上Cx43蛋白的表达水平明显低于缺血再灌注损伤组(P〈0.01)。结论 E2能够下调缺血再灌注损伤后肾叶间动脉平滑肌细胞Cx43蛋白的表达,抑制缝隙连接(GJ)功能,从而降低血管紧张度,促进血管舒张,有效减轻肾缺血再灌注损伤,改善肾功能。
Objective To investigate the effect of estrogen (E2) on the connexin43 (Cx43) expression of renal interlobar arteries after renal ischemia-reperfusion injury (I/R). Methods The experiment was carried out in vivo using an SD rat I/R model. SD rats were randomly divided into normal group, sham-operation group, I/R group, and estrogen-intervention group. The functional changes of the kidney were analyzed after 24 hours of I/R; nephridial tissue section was stained by hematoxylin-eosin (HE), and Puller scores were used to evaluate the degree of kidney damage. Pressure myography was utilized to detect the vasomotor function of renal interlobar arteries. Immunofluorescence technique, qRT-PCR and Western blot were applied to determine the expression of Cx43 in renal interlobar arteries in different groups. Results Estrogen markedly decreased the levels of Cr and BUN in the serum of I/R rats (P〈0.05), and the damage of the kidney tissue could be improved noticeably. The vasomotor rate of renal interlobar arteries was (24. 80±3.70)% after I/R and (41.60±3.50)% after treatment with estrogen, which was higher than that of I/R group (P〈0.05). The expression of Cx43 was lower in renal interlobar arteriesof estrogen-intervention group than that in I/R group (P〈0. 01). Conclusion Estrogen may reduce vascular tension and boost dilation of the artery by inhibiting Cx43 expression and GJ function. Therefore, estrogen may attenuate the damage of I/R and improve renal function.