肾疏宁方对腹膜纤维化大鼠腹膜组织细胞外基质积聚的影响

目的 观察中药肾疏宁方对腹膜纤维化大鼠腹膜功能、腹膜组织细胞外基质（extracellular matrix，ECM）积聚、转化生长因子β1（transforming growth factor β1，TGF-β1）及基质金属蛋白酶抑制剂－1（tissue inhibitor of metalloproteinase-1，TIMP-1）表达的影响。方法 采用腹膜透析液加红霉素注射法诱发SD大鼠腹膜透析腹膜纤维化模型，依体重随机分为4组，1.50%腹膜透析液模型组（B组）、1.5%腹膜透析液加肾疏宁方干预组（C组）、4.25%腹膜透析液模型组（D组）及4.25%腹膜透析液加肾疏宁方干预组（E组），每组各15只，另设空白对照组（A组，15只）。C组及E组予肾疏宁方［43.93 g/（kg？d）］灌胃，A、B、D组予等量生理盐水灌胃。检测腹腔液葡萄糖浓度，计算超滤量（ultra filtration volume， UF）及葡萄糖转运量（mass transfer of glucose，MTG）。观察腹膜病理形态学改变，分析腹膜胶原纤维分布、纤维母细胞计数、Ⅰ型胶原（collagen Ⅰ，Col Ⅰ）及TGF-β1、TIMP-1表达。结果 治疗第6周末，C组及E组腹膜透析腹膜纤维化大鼠UF分别为（－3.3±14.2）mL、（－2.0±10.7）mL，MTG分别为（18.1±0.8） mmol/kg、（16.1±1.2）mmol/kg，腹膜胶原纤维分布分别为（4 721.3%±541.0%）、（6 502.7%±877.4%），纤维母细胞分别为（0.087±0.010）个/mm2、（0.131±0.042）个/mm2，Col Ⅰ分别为（187.5%±36.9%）、（289.7%±95.6%），TIMP-1分别为（2.57%±0.94%）、（3.63%±0.29%），TGF-β1分别为（104.0±20.7）ng/L、（108.2±17.5）ng/L，与同浓度透析液组比较，差异有统计学意义（P〈0.05， P〈0.01）。结论 肾疏宁方可能通过抑制TGF-β1、TIMP-1表达，阻抑ECM过度积聚，进而延缓腹膜透析大鼠腹膜纤维化进展。

Effect of Shenshuning Recipe on the Extracellular Matrix Accumulation of the Peritoneal Fibrosis Rats

Objective To observe the effect of Shenshuning Recipe （SR） on the peritoneal func- tion,accumulation of extracellular matrix （ECM）, and the expression of transforming growth factor-~l （TGF-131 ） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in the peritoneal fibrosis rats. Methods The peritoneal fibrosis correlating peritoneal dialysis SD rat model was induced by injecting erythromycin and peritoneal dialysate. They were randomly divided into 4 groups according to body weight, i.e., the 1.50 % peritoneal dialysate group （ Group B ）, the 1.50 % peritoneal dialysate ＋ SR group （ Group C） ,the 4.25% peritoneal dialysate group （Group D） ,and the 4.25% peritoneal dialysate ＋SR group （Group E）, 15 in each group.Besides,another 15 rats was taken as the blank control group （n =15, Group A）. SR at the daily dose of 43.93 g/kg was given to rats in Group C and E by gastrogavage, while equal volume of normal saline was given to rats in other groups by gastrogavage. The changes of glucose in the peritoneal fluid were detected. The ultra filtration volume （UF）and mass transfer of glucose （MTG）were calculated. The pathomorphological changes of the peritoneum were observed.The distribution of collagen fiber,fibroblast count,collagen β1 （Col β）, expressions of TIMP-1 and TGF-β1were determined. Results At the end of the 6th week ,statistical difference was shown in UF （ -3.3 ±14.2）mL]and （ -2.0±10.7）mL], MTG（18.1 ±0.8） mmol/kg] and（16.1 ±1.2） mmol/kg],collagenfiber（4 721.3±541.0）%]and （6 502.7 ±877.4）%],fibroblast（0.087±0.010）/mm2]and（0.131 ±0.042）/mm2],col （187.5± 36.9 ） % ] and （289.7± 95.6 ） % ], TIMP-1 （2.57 ± 0.94 ） % ] and （3.63 ± 0.29 ） % ], and TGF-β1 （ 104.0 ± 20.7）ng/L]and （108.2 ±17.5）ng/L]between Group C and Group E, when compared with the peritoneal dialysate group at the same concentration （P 〈0.05,P 〈0.01 ）. Conclusion SR could postpone the development of peritoneal fibrosis in peritoneal dialysis SD rats possibly through inhibiting expressions of TGF-β1 and TIMP-1 ,and hindering the over-accumulation of ECM.