益肾颗粒对糖尿病肾病大鼠肾组织Ⅳ型胶原、层黏连蛋白及纤维黏连蛋白表达的影响

Effects of Yishen granule on expression of type Ⅳ collagen. LN and FN in diabetic rats with nephropathy

目的观察益肾颗粒对糖尿病肾病大鼠肾组织Ⅳ型胶原、层黏连蛋白、纤维黏连蛋白表达的影响，探讨其肾脏保护作用机制。方法建立单侧肾切除链脲佐菌素Ⅰ型糖尿病肾病大鼠模型，试验分为正常组、单切肾组、DN模型组、益肾颗粒低剂量组（8．1g／kg）、益肾颗粒高剂量组（16．2g／kg）、洛汀新组（O．0015g／kg）；正常组、单切肾组、DN模型组给予等体积蒸馏水，均灌胃给药，1次／d，连续16周。观察大鼠肾组织Ⅳ型胶原、层黏连蛋白、纤维黏连蛋白表达及肾小球形态学改变。结果正常组、单切肾组、DN模型组、益肾颗粒低剂量组、益肾颗粒高剂量组、洛汀新组的Ⅳ型胶原分别（1521．22±415．26）、（1579．22±343．26）、（3402．00±863．39）、（2984．30±674．53）、（2959．15±561．22）、（2918．04±363．96）：层黏连蛋白表达分别为（1968．04±522．17）、（2004．52±417．19）、（3299．04±665．78）、（3116．89±540．10）、（2932．63±528．38）、（2815．89±798．58）；纤维黏连蛋白表达分别为（2614．67±533．82）、（2742．63±562．80）、（3311．41±529．29）、（2993．44±548．66）、（2953．30±535．74）、（2897．41±505．84）。益肾颗粒高、低剂量组均可下调肾组织、层黏连蛋白及纤维黏连蛋白的表达，降低三者累积光密度值（均P〈0．05），减轻肾小球系膜细胞、系膜基质增生及系膜区纤维化程度，缩小球囊腔扩张，使毛细血管变清晰，减轻内皮下基底膜增生，有改善肾小球的病理变化作用，并以高剂量组更显著。结论益肾颗粒对糖尿病肾病模型大鼠的治疗作用可能与抑制。肾组织Ⅳ型胶原、层黏连蛋白及纤维黏连蛋白的表达有关。

Objective To investigate the influence of Yishen granule on the expression of type Ⅳ collagen, laminin （LN）and fibronectin （FN）in diabetic nephropathy （DN） rats. Methods DN model rats were established by unilateral nephrectomy and intraperltoneal injection of STZ. The experimental rats were divided into six groups： normal group, DN model group, Yishen granule groups in low and high dose （8.1 g/kg, 16.2 g/kg） and positive control medicine group with lotensin （0.0015 g/kg）. After 16 weeks of treatment, kidney tissues were sampled and pathologically observed through Masson trichrome staining. The proteins of type Ⅳ collagen, LN and FN were determined through immunohistochemical methods. Results The type Ⅳ collagen in normal group, DN model group, Yishen granule groups in low and high dose, and positive control medicine group was （1521.22 ± 415.26）, （1579.22± 343.26）, （3402.00± 863.39）, （2984.30 ± 674.53）, （2959.15± 561.22）, （2918.04±363.96）; LN was （1968.04±522.17）, （2004.52±417.19）, （3299.04±665.78）, （3116.89±540.10）, （2932.63±528.38）, （2815.89±798.58）; FN was（2614.67±533.82）, （2742.63±562.80）, （3311.41±529.29）, （2993.44± 548.66）, （2953.30 ± 535.74）, （2897.41 ± 505.84） respectively. The level of type Ⅳ collagen, LN and FN expression in Yishen granule group obviously decreased as compared with that in DN model group （P〈 0.05）. The mesangial cells, basement membrane thickening and endocapillary proliferation in glomerular filtration membrane were significantly alleviated in Yishen granule group. The pathology of kidney was obviously modulated by Yishen granule. Conclusion Yishen granule can significantly inhibits the expressionof type Ⅳcollagen, LN and FN in DN rats, which may be the mechanisms for Yishen granule in protecting the DN rat＇s kidney.