阿巴西普对大鼠2型糖尿病肾病的治疗作用

The role of abatacept in the treatment of type 2 diabetic nephropathy in rats

目的 探讨阿巴西普对大鼠糖尿病肾病的治疗作用.方法 以2型糖尿病肾病大鼠为研究对象,2型糖尿病肾病大鼠30只平均分为阿巴西普组、糖尿病肾病组,每组15只,另设正常对照组15只.阿巴西普组给予阿巴西普干预.阿巴西普干预8周后,检测血液生化指标、肾动脉主干血流参数、肾实质弹性、肾组织损伤情况、足细胞结构改变,以及肾实质组织中CD31、CD34、podocin、nephrin、B7-1的表达情况.结果 糖尿病肾病组和阿巴西普组的空腹血糖、肌酐清除率、24 h尿白蛋白排泄率、肾小球肥大指数均高于对照组（均P〈0.05）;阿巴西普组的肌酐清除率、24 h尿白蛋白排泄率、肾小球肥大指数均低于糖尿病肾病组（均P〈0.05）.肾动脉主干血流收缩期峰值流速、舒张末期流速和平均流速,由低到高依次为糖尿病肾病组、阿巴西普组、空白对照组（均P〈0.05）;肾动脉主干血流收缩期加速度、搏动指数和阻力指数,由高到低依次为糖尿病肾病组、阿巴西普组、空白对照组（均P〈0.05）.肾弹性评分由高到低依次为糖尿病肾病组、阿巴西普组、空白对照组（P〈0.05）.阿巴西普组和糖尿病肾病组大鼠肾脏实质的CD31和CD34的表达无明显差异（均P〉0.05）,但都高于正常对照组（均P〈0.05）.podocin和nephrin蛋白表达由高到低依次为正常对照组、阿巴西普组、糖尿病肾病组（均P〈0.05）.B7-1蛋白表达由低到高依次为正常对照组、阿巴西普组、糖尿病肾病组（P〈0.05）.结论 阿巴西普可明显改善2型糖尿病肾病大鼠的肾脏损害.

Objective To observe the role of abatacept in the treatment of diabetic nephropathy in rats. Methods Type 2 diabetic nephropathy rat model was established, and was randomly divided into abatacept group and non-intervention group, 15 each. 15 normal rats were served as control group （ NC） . The abatacept group was given abatacept for 8 weeks. The control group was set at the same time period. Then the blood biochemical indexes, blood flow parameters of renal main artery, elasticity of renal parenchymal, HE staining of renal parenchymal and ultrastructure of podocytes were all evaluated. The expression of CD31, CD34, podocin, nephrin, and B7-1 in renal parenchyma were detected. Results Compared to the NC group, the fasting blood glucose, creatinine clearance rate, urine albumin excretion rate, and kidney hypertrophy index in the non-intervention and abatacept groups were significantly increased （P〈0. 05）;creatinine clearance rate, urine albumin excretion rate, and kidney hypertrophy index in the abatacept group were significantly lower compared to the non-intervention group （P〈0. 05）. There were significant differences in peak systolic velocity, end diastolic velocity, and mean velocity among these 3 groups, and these differences were ranked as non-intervention group〈abatacept group〈control group （ P〈0. 05 ）; there were significant differences in systolic acceleration, pulsatility index, and resistance index among these three groups, with the differences ranked as non-intervention〉abatacept〉control groups （P〈0. 05）. There were significant differences in the stiffness of kidneys among these three groups, with the differences ranked as non-intervention〉abatacept〉control groups （P〈0. 05）. HE staining and transmission electron microscope observation showed that there were obvious changes in the renal parenchyma of rats in the non-intervention group and the abatacept group, and the changes of kidney in the non-intervention group were worse than those in the abatacept group. CD31 and CD34 expression in kidney parenchyma of rats in the abatacept group and non-intervention group were higher than those in the control group, the abatacept group and non-intervention group〉the control group （P〈0. 05）, while no significant differences between the abatacept group and non-intervention group in CD31 and CD34 expression （P〉0. 05）. There were significant differences in podocin and nephrin expression in kidney parenchyma of rats among these three groups, and these differences were ranked as the control〉abatacept〉non-intervention groups （P〈0. 05）. There were significant differences in B7-1 expression in kidney parenchyma of rats among these three groups, and these differences were ranked as the control〈abatacept〈non-intervention groups （P〈0. 05）. Conclusion Abatacept may significantly alleviate the renal injury in type 2 diabetic nephropathy rats.