Na Yu, Zhang Xiao-xuan, Zhang Xiao-dong, Yuan Hong-ping, Hu Xiu-li, Zheng Wei, Li Gen
Department of Nephrology, the Fourth Hospital, Jilin University, Changchun, Jilin, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Dec;19(12):735-8.
To explore therapeutic effect of glutathione (GSH) on unilateral ureteral obstruction (UUO) induced renal interstitial fibrosis and its mechanism in rat.
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 anti-oxygen 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.
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 membrane 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 [Hyp: (0.524+/-0.132) microg/mg, T-AOC: (1.48+/-0.21) U/mg, T-SOD: (12.77+/-0.76) U/mg, MDA: (2.65+/-0.32) nmol/mg, all P<0.01]. Compared with UUO group, pathological changes were milder and the contents of Hyp [(1.598+/- 0.252) microg/mg vs. (1.027+/-0.196) microg/mg, P<0.05] and MDA [(4.58+/-0.59) nmol/mg vs. (3.26+/- 0.34) nmol/mg, P<0.05] were significantly decreased in kidney of GSH group, meanwhile the content of T-AOC was increased [(0.67+/-0.19) U/mg vs. (0.94+/-0.17) U/mg, P<0.05], but the content of T-SOD did not show any change [(9.39+/-0.87) U/mg vs. (9.41+/-0.93) U/mg, P>0.05].
Reduced glutathione treatment attenuates UUO-induced renal interstitial fibrosis via decreasing content of Hyp in UUO kidney and preventing oxidation stress injury.
探讨谷胱甘肽（GSH）对单侧输尿管梗阻（UUO）诱导的大鼠肾间质纤维化的治疗作用及其机制。
将36只成年健康Wistar大鼠随机分为3组（每组n = 12）：假手术组、UUO组和GSH组。按先前所述方法对UUO组和GSH组大鼠进行左侧单侧输尿管结扎。假手术组大鼠的输尿管仅作处理但不结扎。在GSH组中，于UUO前一天根据动物体重以不同剂量腹腔注射GSH（100 mg·kg⁻¹·d⁻¹），并在UUO后连续10天注射。同时，假手术组和UUO组给予与GSH组相同体积的生理盐水。术后10天处死动物。用苏木精-伊红（HE）和Masson染色观察梗阻肾组织的病理变化。采用化学比色法测定羟脯氨酸（Hyp）含量和总抗氧化能力（T-AOC），用改良的黄嘌呤/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。
UUO术后10天，可见梗阻肾肾实质肿胀和萎缩。间质中纤维物质和单核细胞浸润增加。此外，可见肾小管基底膜间质增厚和肾皮质间质增宽。还观察到近曲小管肥大或萎缩。部分肾小管内有细胞或白蛋白管型。UUO术后10天梗阻肾出现间质纤维化。数据表明，与假手术组相比，输尿管梗阻显著增加了Hyp和MDA含量，但降低了T-AOC含量和T-SOD活性[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，均P<0.01]。与UUO组相比，GSH组肾脏病理变化较轻，Hyp含量[（1.598±0.252）μg/mg对（1.027±0.196）μg/mg，P<0.05]和MDA含量[（4.58±0.59）nmol/mg对（3.26±0.34）nmol/mg，P<0.05]显著降低，同时T-AOC含量增加[（0.67±0.19）U/mg对（0.94±0.17）U/mg，P<0.05]，但T-SOD含量无变化[（9.39±0.87）U/mg对（9.41±0.93）U/mg，P>0.05]。
还原型谷胱甘肽治疗通过降低UUO肾脏中Hyp含量和预防氧化应激损伤减轻UUO诱导的肾间质纤维化。
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