苯那普利对腹膜纤维化大鼠的腹膜功能及转化生长因子-β_1的影响

Impact of benazepril on peritoneal function and TGF-β_1 in peritoneum of peritoneal fibrotic rat model

目的研究苯那普利对腹膜纤维化大鼠腹膜功能及转化生长因子(TGF)-β1的影响,探讨苯那普利对腹膜纤维化的作用及可能的机制。方法 48只雄性Wistar大鼠,随机分成3组:对照组、模型组、苯那普利治疗组,每组16只。对照组给予腹腔注射生理盐水,模型组腹腔注射4.25%透析液+红霉素建模,苯那普利治疗组在与模型组同样方法建模后腹腔注射苯那普利治疗。3组均在腹腔注射后第6周行超滤量测定;然后处死,进行2h腹膜平衡试验(PET)评价腹膜功能;并取壁层腹膜应用免疫组化方法测定纤维连接蛋白(FN)及TGF-β1的表达水平。结果与对照组比较,模型组、苯那普利治疗组的腹膜超滤量均明显减少(P均<0.05),且苯那普利治疗组的超滤量高于模型组[(6.83±0.46)vs(0.60±0.40)ml,P<0.05];模型组、苯那普利治疗组透析液尿素浓度(D)与血浆尿素浓度(Purea)比值(D/Purea)均明显增高(P均<0.05),且苯那普利治疗组的D/Purea低于模型组(0.61±0.04vs0.82±0.49,P<0.05)。与对照组比较,模型组、苯那普利治疗组的TGF-β1及FN的表达率均明显增加(P均<0.05),且苯那普利治疗组TGF-β1[(47.99±2.81)%vs(66.88±1.91)%,P<0.05]及FN的表达率[(56.27±3.57)%vs(71.87±3.86)%,P<0.05]均低于模型组。结论苯那普利能够改善腹膜纤维化大鼠的腹膜功能,其机制可能是通过使腹膜组织中TGF-β1的表达水平下降,减少FN的积聚,从而减轻腹膜纤维化。

Objective To observe the impact of benazepril on peritoneal function and transforming growth factor（TGF）-βt in peritoneum of peritoneal fibrotic rats and explore the effect of benazepril on peritoneal fibrosis and its potential mechanism. Methods Forty-eight healthy male Wistar rats were randomly divided into 3 groups （ n = 16 each） ：control group ,model group and benazepril treatment group. Intra-peritoneal injection of normal saline was giv- en in control group; intra-peritoneal injection of 4.25% dialysate plus erythromycin was administered to establish peritoneal fibrotic rat model in model group;benazepril treatment was given after establishing model of same with model group method in benazepril treatment. After six weeks, ultrafiltration volume was detected, then the rats were killed and two-hour peritoneal equilibration test （2 h PET） was measured for assessing peritoneal functions. Taking parictal peritoneum,the expression levels of fibronectin（FN） and TGF-IM were determined by immunohistochemistry method. Results Compared with control group, the peritoneal ultrafihration volume in model group and benazepril treatment group significantly decreased （ all P 〈 0. 05 ）, and the peritoneal ultrafiltration volume in benazepril treat-ment group was higher than that in model group [ （ 6.83 ± 0.46 ） vs （ O. 60 ± 0. 40 ） ml, P 〈 0.05 ]. Compared with control group,the ratio of dialysate urea concentration to plasma urea concentration（D/Purea） in model group and benazepril treatment group significantly increased （ all P 〈 0.05 ）, and D/Purea in benazepril treatment group was lower than that in model group （0.61 ± 0.04 vs 0. 82 ± 0.49, P 〈 0.05 ）. Compared with control group, the expression levels of TGF-β1 and PN in model group and benazepril treatment group significantly increased（ all P 〈 0. 05 ）, and the expression levels of TGF-β1 [ （47.99 ± 2.81 ） % vs （ 66.88 ± 1.91 ） % , P 〈 0.05 ] and FN [ （ 56.27 ± 3.57 ） % vs （71.87 ± 3.86） %, P 〈 0.05 ] in benazepril treatment group were all lower than those in model group. Conclusion Benazepril can improve the peritoneal functions of rats with peritoneal fibrosis, and its mechanism might be associ-ated with lightening peritoneal fibrosis possibly through lowering expression of TGF-β1 and decreasing excessive dep-osition of PN.