G蛋白偶联雌激素受体可通过抑制氧化应激反应减轻肾缺血再灌注损伤

G protein-coupled estrogen receptor alleviates renal ischemia reperfusion injury by inhibiting oxidative stress

目的探讨G蛋白偶联雌激素受体(G protein-coupled estrogen receptor,GPER)对氧化应激反应的影响,及其对肾缺血再灌注损伤的保护作用和可能机制。方法将雌性SD大鼠去卵巢后随机分为去卵巢组(OVX)、肾缺血再灌注组(OVX+I/R)、雌激素干预组(OVX+I/R+E2)、GPER特异性激动剂G1干预组(OVX+I/R+G1)、雌激素+GPER特异性阻断剂G15干预组(OVX+I/R+G15+E2)(每组8只)。测定各组大鼠血肌酐(Cr)和尿素氮(BUN)水平,HE染色观察肾组织病理性形态,检测各组肾组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,Western blot检测肾组织p-PI3K、p-Akt蛋白的表达水平。结果与OVX组相比,OVX+I/R组血Cr和BUN水平升高(P<0. 01),肾组织病理损伤(HE染色)明显(P<0. 01),氧化应激反应加重(P<0. 01),p-PI3K、p-Akt蛋白表达水平显著降低(P<0. 01);与OVX+I/R组相比,E2和G1干预组血Cr和BUN水平降低(P<0. 01),肾组织病理损伤减轻(P<0. 01),氧化应激反应减轻(P<0. 01),p-PI3K、p-Akt蛋白表达水平升高(P<0. 01),而GPER特异性阻断剂G15可部分消除E2对肾缺血再灌注损伤的保护作用。结论 E2和GPER激动剂G1可降低氧化应激反应,减轻大鼠肾缺血再灌注损伤,且E2对I/R的保护作用可能通过GPER介导,其机制可能涉及PI3K/Akt信号通路的激活。

Objective To investigate the effect of the G protein-coupled estrogen receptor(GPER)on oxidative stress and its possible mechanisms for reducing renal ischemia reperfusion injury.Methods Female ovariectomized rats were divided into the ovariectomy(OVX),renal ischemia reperfusion(OVX+I/R),estrogen intervention(OVX+I/R+E2),GPER-specific agonist(G1)intervention(OVX+I/R+G1),and estrogen+GPER specific blocker G15 intervention(OVX+I/R+G15+E2)groups(n=8 rats per group).Serum creatinine(Cr)and urea nitrogen(BUN)levels were measured,and histopathological examination using hematoxylin and eosin(HE)staining was used to observe the pathological morphology of the renal tissues.Superoxide dismutase and malondialdehyde activities were detected,and Western blot was used to observe p-PI3K and p-Akt expressions in the renal tissues of each group.Results Compared with the OVX group,serum Cr and BUN levels were increased,pathological damage to the renal tissue was significant,oxidative stress was aggravated,and p-PI3K and p-Akt protein expression levels were significantly decreased in the OVX+I/R group(all P<0.01).Compared with the OVX+I/R group,the serum Cr and BUN levels were decreased,renal tissue pathological damage was reduced,oxidative stress was reduced,p-PI3K and p-Akt protein expressions were increased(all P<0.01),and the GPER-specific inhibitor,G15,partially eliminated the protective effect of E2 on renal ischemia reperfusion injury in the E2 and G1 intervention groups.Conclusions During renal ischemia reperfusion injury,E2 and G1 may reduce oxidative stress to alleviate the injury.GPER may mediate the protective effect of E2,and its mechanism may involve activating the PI3K/Akt signaling pathway.