枸杞多糖对UUO模型大鼠氧化应激反应和肾间质纤维化的影响及保护机制

发布时间：2018-05-20 14:31

本文选题：枸杞多糖 + 氧化应激　；参考：《宁夏医科大学》2017年硕士论文

【摘要】：目的:观察不同剂量枸杞多糖(LBP)对单侧输尿管梗阻(UUO)模型大鼠氧化应激及肾间质纤维化的影响,探讨其对肾脏纤维化的保护机制。方法:将144只SPF级健康成年雄性SD大鼠随机分为假手术组、UUO模型组、LBP低剂量组、LBP中剂量组、LBP高剂量组和贝那普利组。除假手术组外,UUO模型组和LBP低、中、高剂量组及贝那普利组均行采用经典UUO手术进行造模,术后1天开始,连续灌胃给药3周,其中低、中、高剂量LBP组分别按照LBP 400mg·(kg·d)-1、600mg·(kg·d)-1、800mg·(kg·d)-1灌胃给药;贝那普利治疗组给药1.05mg·(kg·d)-1,假手术组和UUO模型组予以生理盐水等量灌胃。在术后第3、7、14、21天每组各处死6只大鼠,采集血标本检测血清肌酐(Scr);计算肾脏脏器指数;取梗阻侧(左)肾组织行HE染色和Masson三色染色,观察光镜下的病理变化;ELISA法和比色法检测血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)及转化生长因子β-1(TGF-β1)的水平。结果:(1)与假手术组比较,造模组各时间点Scr及肾脏脏器指数均有不同程度的升高(P0.05),提示造模成功。(2)HE染色和Masson三色染色示,假手术组左肾组织结构正常;UUO模型组左肾组织随时间的延长肾小管的病变逐渐加重,间质内炎性细胞浸润由少到多,造模21天时可见灶状纤维化;(3)与UUO模型组比较,LBP低、中、高剂量组及贝那普利组的肾脏脏器指数均有不同程度的下降。造模后7、14、21天时LBP低、中、高剂量组血清MDA水平均低于UUO模型组(P0.05);各时间点SOD、GSH-PX含量均高于UUO模型组(P0.05),且以LBP中剂量组的效果最明显。(4)LBP低、中、高剂量组及贝那普利组的血清TGF-β1水平明显低于UUO模型组(P0.05),以LBP中剂量组和贝那普利组的效果最明显。(5)与UUO模型组相比较,LBP低、中、高剂量组及贝那普利组肾间质中炎性浸润及肾小管损伤较轻,间质纤维化程度不重。结论:(1)枸杞多糖能够减少UUO模型大鼠血清中MDA等氧化应激产物的释放、增加SOD、GSH等抗氧化因子的生成。(2)枸杞多糖能够减轻UUO模型大鼠肾小管间质的病理改变,减慢肾间质纤维化的程度。(3)枸杞多糖能够降低UUO模型大鼠血清中TGF-β1的水平,可能由此抑制肾间质纤维化,延缓CKD的进展。
[Abstract]:Aim: to observe the effects of different doses of Lycium barbarum polysaccharides LBPon on oxidative stress and renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to explore the protective mechanism of LBPon on renal fibrosis. Methods: a total of 144 adult male SD rats of SPF grade were randomly divided into two groups: sham operation group (UUO model group), low dose group (LBP medium dose group) and benazepril group (high dose group and benazepril group). With the exception of sham-operated group, UUO model group and low LBP group, high dose group and benazepril group were all treated with classical UUO operation. The high dose LBP group was treated with LBP 400mg / kg d)-1600mg / kg d)-1800mg / kg / d ~ (-1), the benazepril group was given 1.05mg / kg / d ~ (-1), the sham operation group and UUO model group were given the same amount of normal saline. Six rats were killed in each group on day 3, 7, 14, 21 after operation. Blood samples were collected to detect serum creatinine (creatinine), renal organ index (CRI) was calculated, HE staining and Masson trichrome staining were performed in the left (left) renal tissue of the obstruction side. The pathological changes under light microscope were observed. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and transforming growth factor 尾 -1 (TGF- 尾 1) in serum were determined by Elisa and colorimetry. Results compared with sham-operation group, Scr and renal organ index in model group increased in different degrees (P 0.05), indicating that the model was successfully made by HE staining and Masson trichrome staining. The pathological changes of left renal tubules in the sham-operated group with normal left renal tissue structure increased gradually with the prolongation of time, and the infiltration of inflammatory cells in the interstitial tissue increased from less to more. The focal fibrosis was observed in the model group at 21 days.) compared with the UUO model group, the pathological changes of the left renal tissue in the UUO model group were lower and more moderate than those in the UUO model group. The renal organ index of high dose group and benazepril group were decreased to some extent. The serum MDA level in the middle and high dose groups was lower than that in the UUO model group (P 0.05), the content of GSH-PX in the UUO model group was higher than that in the UUO model group at each time point, and the effect of LBP medium dose group was the most obvious. The serum levels of TGF- 尾 1 in the high dose group and benazepril group were significantly lower than those in the UUO model group (P 0.05). The effect of LBP medium dose group and benazepril group was the most obvious. (5) compared with the UUO model group, the serum TGF- 尾 1 level in the high dose group and benazepril group was lower and lower than that in the UUO model group. In high dose group and benazepril group, inflammatory infiltration and tubulointerstitial injury were mild and interstitial fibrosis was not serious. Conclusion Lycium barbarum polysaccharides can reduce the release of oxidative stress products such as MDA in the serum of UUO model rats, and increase the production of antioxidant factors such as SDS-GSH. 2) LBP can reduce the pathological changes of renal tubulointerstitium in UUO model rats. LBP could reduce the level of TGF- 尾 1 in serum of UUO model rats, which may inhibit renal interstitial fibrosis and delay the progress of CKD.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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