还原型谷胱甘肽对单侧输尿管梗阻大鼠羟脯氨酸及氧化应激反应的影响  

Effects of reduced glutathione on contents of hydroxyproline and oxidation stress reaction in kidney of unilateral ureteral obstruction in rat

作　　者：那宇[1] 张晓暄[1] 张晓东[1] 袁洪萍[1] 胡秀丽[1] 郑伟[1] 李根[1] 

机构地区：[1]吉林大学第四医院肾内科,长春130011

出　　处：《中国危重病急救医学》2007年第12期735-738,I0002,共5页Chinese Critical Care Medicine

基　　金：吉林省长春市科技计划资助项目（04-07SF036）

摘　　要：目的采用单侧输尿管梗阻（UUO）致肾间质纤维化大鼠模型，探讨还原型谷胱甘肽（GSH）抗肾间质纤维化的部分作用机制。方法健康Wistar大鼠36只，随机分为假手术（Sham）组、模型组（UUO组）和GSH组，每组12只。UUO组和GSH组大鼠麻醉后开腹分离左侧输尿管，并于靠近。肾盂段行左输尿管结扎；Sham组开腹但不行输尿管结扎。GSH组于术前1d腹腔注射GSH100mg·kg^-1·d^-1，连续给药10d；Sham组和UUO组给予等量生理盐水。术后10d处死各组大鼠，取左侧肾脏，行苏木素-伊红（HE）和Masson染色，观察大鼠。肾脏组织病理学的改变；用化学比色法测定梗阻侧肾组织羟脯氨酸（Hyp）含量和总抗氧化能力（T-AOC），用黄嘌呤氧化酶法测定总超氧化物歧化酶（T-SOD）活性；用硫代巴比妥酸法测定丙二醛（MDA）含量。结果大鼠行UUO 10d后，梗阻侧肾脏肿大、肾实质变薄，肾间质水肿，弥漫性炎细胞浸润，肾小管扩张或萎缩，部分肾小管腔内有蛋白或细胞管型，间质趋向纤维化。与Sham组比较[Hyp（0．524±0．132）μg／mg，T-AOC（1．48±0．21）U／mg，T-SOD（12．77±0．76）U／mg，MDA（2．65±0．32）nmol／mg]，UUO组与GSH组梗阻侧肾脏病理改变明显，且。肾组织中Hyp、MDA含量增加，T-AOC降低，T-S0D活性下降（P均〈0．01）。与UUO组比较，GSH组梗阻侧肾脏组织病理学改变减轻，且肾组织中Hyp含量减少[（1．598±0．252）μg／mg比（1．027±0．196）μg／mg，P〈0．053，T-AOC升高[（0．67±0．19）U／mg比（0．94±0．17）U／mg，P〈0．05]，MDA含量降低[（4．58±0．59）nmol／mg比（3．26±0．34）nmol／mg，P〈0．05]，T-SOD活性无明显变化[（9．39±0．87）U／mg比（9．41±0．93）U／mg，P〉0．05]。结论GSH可缓解UUO大鼠肾间质纤维化病理改变，降低梗阻侧。肾脏Hyp含量与其抗氧化应激作用，减轻UUO诱导的氧化损伤。Objective To explore therapeutic effect of glutathione （GSH） on unilateral ureteral obstruction （UUO） induced renal interstitial fibrosis and its mechanism in rat. Methods Thirty -six adult healthy Wistar rats were randomly divided into 3 groups （each n= 12）： sham operation group, UUO group and GSH group. Rats in UUO group and GSH group underwent left unilateral ureteral ligation as described previously. Rats in sham group had their ureters manipulated but not ligated. In GSH group, GSH was injected intraperitoneally （100 mg·kg^-1 · d^-1） in different doses based on the animal＇s body weight, one day before UUO and then for consecutive 10 days after UUO. Meantime, same volume of physiological saline was given in sham operation and UUO groups as GSH group. Animals were sacrificed at 10 days after surgery. The pathological changes in obstructed kidney tissue were observed with hematoxylin and eosin （HE） and Masson stains. The contents of hydroxyproline （Hyp） and total antioxygen capability （T-AOC） were measured by chemical colorimetry method, the activity of total superoxide dismutase （T- SOD） was assayed by a modified xanthine/xanthine oxidase method, and the content of malondialdehyde （MDA） was determined by thiobarbituric acid method. Results Ten days after UUO, swelling and atrophy in renal parenchyma of obstructed kidneys were clearly observed. Fibrous material and monocyte infiltration were increased in the interstitial space. Furthermore, thickening of interstitial space of the tubular basement memberance and widening of the interstitial space of the renal cortex were noted. Hypertrophy or atrophy of juxtaglomerular tubules were also observed. There were cellular or albumin casts in a part of tubules. Interstitial fibrosis was observed in obstructed kidneys 10 days after UUO. The data indicated that ureteral obstruction significantly increased the contents of Hyp and MDA, but decreased the content of T -AOC and T-SOD activity, as compared with sham operation group [Hy

关 键 词：还原型谷胱甘肽 单侧输尿管梗阻 纤维化 肾间质 羟脯氨酸 氧化应激 

分 类 号：R686[医药卫生—骨科学]