罗格列酮对大鼠腹膜透析相关性腹膜纤维化的影响  

Influence of rosiglitazone on peritoneal fibrosis induced by peritoneal dialysate in rats

作　　者：林沁[1] 邹忠东[2] 项协隆[1] 韦永光[1] 郑丰[1] 

机构地区：[1]南京军区福州总医院肾内科,福州350025 [2]南京军区福州总医院普通外科,福州350025

出　　处：《第二军医大学学报》2011年第2期144-149,共6页Academic Journal of Second Military Medical University

基　　金：福建省科技厅重点资助项目(2008Y0085)~~

摘　　要：目的观察罗格列酮(rosiglitazone,RGZ)对腹膜透析所致腹膜纤维化的影响。方法 50只SD大鼠随机分为6组:空白对照组(n=5)、生理盐水(NS)组、模型组、二甲亚砜(DMSO)组、低浓度RGZ组、高浓度RGZ组(后5组n=9)。除空白对照组外其余大鼠均置入腹透管,除空白组和NS组外其余组均采用高糖腹膜透析液+红霉素制作慢性腹膜透析无菌性腹膜纤维化的大鼠模型。DMSO组、低浓度RGZ组、高浓度RGZ组分别采用DMSO、1.5mg/kg RGZ、15mg/kg RGZ治疗。透析5周后行1h腹膜平衡试验,检测血糖及血脂,计算超滤量(UF)、初始腹透液与透出液葡萄糖比值(D1/D0)、透出液与血浆尿素氮比值(D/Purea);处死大鼠,取壁层腹膜行H-E及Masson染色,观察腹膜形态改变,半定量计算腹膜单位面积血管数及炎症细胞数;免疫组化检测腹膜转化生长因子(TGF)-β1和α-平滑肌肌动蛋白(α-SMA)的表达情况。结果与空白对照组相比,模型组和DMSO组间皮下基质增厚,血管增生及炎症细胞浸润增加(P<0.05);TGF-β1、α-SMA表达水平增高(P<0.05);RGZ能改善上述病理改变,下调TGF-β1、α-SMA表达(P<0.05);与空白对照组比较,NS组、模型组、DMSO组、低浓度RGZ组及高浓度RGZ组的超滤量和D1/D0减少,D/Purea增加(P<0.05),其中以DMSO组及模型组改变最为显著。两种剂量RGZ间差异无统计学意义(P>0.05)。结论在大鼠腹膜透析模型中加用罗格列酮能有效保护腹膜功能,抑制腹膜纤维化。Objective To investigate the effect of rosiglitazone （RGZ） in prevention of peritoneal fibrosis induced by peritoneal dialysis in rats. Methods Fifty SD rats were randomly divided into six groups： control group （n= 5）, normal saline （NS） group（n=9）, model group （n=9）, dimethyl sulfoxide（DMSO） group（n 9） , low dose RGZ group （n=9） , and high- dose RGZ group （n 9）. Peritoneal catheters were implanted in the last five groups, and peritoneal fibrosis models were induced in the last four groups by high-glucose peritoneal dialysate and erythromycin with rats. Animals in the low dose RGZ and high-dose RGZ groups were treated with 1. 5 mg/kg RGZ and 15 mg/kg RGZ, respectively. The one hour peritoneal equilibration test was performed and the plasma glucose and serum lipids were estimated five weeks after dialysis. The ultrafiltration volume （UF）, dialysate to-plasma urea ratio （D/Purea）, and glucose reabsorption （D1/Do ） were calculated. The visceral peritoneum tissues of rats were stained with hematoxylin eosin（H-E） and Masson trichrome staining to observe the changes of peritoneal morphology. Blood vessels and leukoeytes of peritoneum were quantified as n/mmz within the histological sections with H E staining. The expression of TGFβ1 and a-SMA in the parietal peritoneum was detected by immunohistochemistry assay. Results Compared with the control group, the numbers of peritoneal vessels, leukocytes, peritoneal thickness, and the expressions of TGF-β1 and α-SMA were significantly higher in the model group and DMSO group （P〈0. 05）. Administration of RGZ improved the above changes and significantly decreased the expression of TGF-β1and α-mSMA in the model and DMSO groups （P〈0.05）. Compared with the control group, the UF and D1/D0 were significantly lower and D/P was significantly higher in the rest five groups （P〈0.05）, and there were no significant differences between the low-dose RGZ group and the high-dose RGZ group（P〈0.05）. Conclusion Ad

关 键 词：罗格列酮 腹膜纤维化 腹膜透析 

分 类 号：R459.51[医药卫生—治疗学]