赖诺普利对腹膜纤维化大鼠腹膜组织TGF-β_1表达的影响

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目的研究赖诺普利对腹膜纤维化大鼠腹膜细胞因子的影响,探讨赖诺普利对腹膜纤维化的作用及可能的机制。方法 36只SD大鼠(6~8周龄,体重180~200g)随机分为3组,每组12只。生理盐水(NS)组:每日腹腔内灌注生理盐水15ml,作为正常对照;模型(PDF)组:每日腹腔内直接注射4.25%含糖透析液15ml,并在第7、14、21、28天加入红霉素6.25万单位,建立腹膜纤维化模型;赖诺普利(LIS)治疗组:与PDF组同样方法建立腹膜纤维化模型,在此基础上,每日每只大鼠灌胃赖诺普利胶囊0.8mg/100g体重进行治疗。上述各组大鼠均于腹腔注射35d后处死;并取壁层腹膜(沿腹中线两侧中部避开注射部位)和脏层腹膜(肠系膜)组织观察其血管计数及组织学改变;用免疫组化方法测定各组的纤维连接蛋白(FN)以及转化生长因子(TGF)-β1的表达水平。结果组织形态学上,PDF组中腹膜组织明显增厚,炎细胞浸润,纤维样物质增生,而LIS治疗组腹膜纤维化程度明显减轻。LIS组大鼠腹膜血管计数较PDF组明显减少[(4.17±1.11)vs(7.33±1.61)个/视野,P<0.05];免疫组化分析,LIS组FN的表达率[(56.21±3.05)%vs(71.51±4.76)%,P<0.05]及TGF-β1的表达率[(48.77±2.68)%vs(66.74±2.47)%,P<0.05]较PDF组均明显减低。结论赖诺普利可下调腹膜组织中TGF-β1的表达,减少细胞外基质FN的积聚,改善腹膜纤维化,发挥保护腹膜的作用。 Objective To study the effect of lisinopril on peritoneal cytokines in rats with peritoneal fibrosis and to explore the effect of lisinopril on peritoneal fibrosis and its possible mechanism. Methods Thirty-six SD rats (6-8 weeks old, weighing 180-200g) were randomly divided into 3 groups with 12 rats in each group. Normal saline (NS) group: daily intraperitoneal injection of saline 15ml, as a normal control; model group (PDF): daily intraperitoneal direct injection of 4.25% sugar dialysate 15ml, and in the first 7,14,21,28 Day 6200 units of erythromycin added to establish a peritoneal fibrosis model; lisinopril (LIS) treatment group: the same method with the PDF group to establish a peritoneal fibrosis model, on this basis, each rat fed stomach Knapley capsules 0.8mg / 100g body weight for treatment. The rats in each group were sacrificed 35 days after intraperitoneal injection, and the vascular counts and histological changes were observed in the peritoneum of the parietal (avoiding the injection site along the middle of both sides of the midline) and the peritoneum (mesentery) of the visceral layer. Methods The levels of fibronectin (FN) and transforming growth factor-β1 (TGF-β1) in each group were determined. Results In histomorphology, peritoneal thickening, inflammatory cell infiltration and fibrous material hyperplasia were found in PDF group, while the degree of peritoneal fibrosis in LIS group was significantly reduced. The number of peritoneal vessels in LIS group was significantly lower than that in PDF group [(4.17 ± 1.11) vs (7.33 ± 1.61) / field, P <0.05]. Immunohistochemical analysis showed that the expression of FN in LIS group was (56.21 ± 3.05) % vs (71.51 ± 4.76)%, P <0.05] and the expression of TGF-β1 [(48.77 ± 2.68)% vs (66.74 ± 2.47)%, P <0.05] Conclusion Lisinopril can down-regulate the expression of TGF-β1 in the peritoneal tissue, reduce the accumulation of extracellular matrix FN, improve peritoneal fibrosis and protect the peritoneum.
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