丁羟茴香醚对衰老大鼠肾脏缺血再灌注损伤的保护作用

目的观察老年大鼠肾脏缺血再灌注（I／R）模型中。肾小管上皮细胞的损伤变化，探讨活性氧（ROS）清除剂对I／R损伤的保护作用。方法27月龄大鼠随机分为假手术组、I／R模型组、丁羟茴香醚（BHA）组和nicardipine组。夹闭双侧。肾动脉30min再灌注18h制成I／R模型。观察肾功能、肾脏病理改变、肾小管上皮细胞凋亡情况。检测肾组织半胱氨酸天冬氨酸蛋白酶（caspase）3、细胞色素C表达。测定肾组织脂质过氧化物丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性。结果（1）肾脏I／R损伤时，老年大鼠肾功能明显减退，肾组织病理改变比较明显，大量肾小管上皮细胞凋亡，肾组织caspase-3、细胞色素C表达明显上调。肾组织中MDA增加、SOD活性下降（P均〈0．05）。（2）BHA或nicardipine均能明显改善肾功能。肾组织病理改变和凋亡相关指标（P〈0．05）；BHA或nicardipine均能减少组织中MDA含量，部分恢复肾组织中SOD含量。结论老年大鼠肾脏I／R损伤时肾小管上皮细胞凋亡增加，肾功能减退。ROS堆积后，线粒体损伤导致肾小管上皮细胞凋亡。清除ROS可以抑制‘肾小管上皮细胞凋亡，减轻I／R损伤。

Protective effect of butylated hydroxyanisole on renal ischemia/reperfusion injury in aging rats

Objective To investigate the apoptosis of tubular cells after renal ischemia/ reperfusion (I/R) injury in aging rats, and the effects of using butylated hydroxyanisole (BHA) to inhibit the products of ROS on the model. Methods Wistar rats aged 27 months were randomly divided into 4 groups, which were sham, I/R model, BHA gavage and nicardipine injection group. The model was established through clamping bilateral renal arteries 30 min for ischemia, and reperfusing them for 18 hours. The time points we chose were based on previous experiments. Renal function, pathological changes, apoptosis were observed, the expression of caspase-3 and Cyc C, the activity of caspase-3 ,MDA volume, activity of superoxide dismutase (SOD)in kidney tissue were examined. Results (1)renal function of all rats slipped following I/R injury, and the pathological changes were severe, and a lot of renal tubular epithelium turned into apoptosis. Expression of caspase-3 and Cyc C as well as MDA volume were increased, the activity of caspase-3 was increased and the activity of SOD was decreased. (2) Either BHA or nicardipine could ameliorate declines in renal function, pathological changes. Either of them could decrease MDA volume and increase the activity of SOD.Conclusions In aging rats, I/R injury leads to elevated ROS accumulation, which leads to progressive apoptosis. Both inhibition of L-type Ca2+ channel and activation of ROS can attenuate apoptosis in tubular cells.