摘要
目的 :探讨维甲酸对大鼠单侧输尿管梗阻 (UUO)模型肾间质肌成纤维细胞增生的影响。方法 :选用36只大鼠建立UUO模型 ,治疗组和对照组各 18只。在建立模型前 2d分别给予 10mg/kg全反式维甲酸或溶媒皮下注射 ,每天一次。观察模型第 3、7、12d肾小管损害百分比、肾间质纤维化程度、肾间质肌成纤维细胞数、肾间质增生肌成纤维细胞数和肾脏TGFβ - 1mRNA表达。 结果 :UUO模型肾间质有显著肌成纤维细胞积聚和局部增生。在UUO模型第 7d ,维甲酸治疗组肾小管损害百分比和肾间质纤维化分值显著低于对照组 [(15 9± 2 0 ) %vs (2 7 3±2 2 ) %和 (0 4 7± 0 12 )vs (1 6 5± 0 18) ,P <0 0 1];而肾间质肌成纤维细胞数和增生肌成纤维细胞数显著低于对照组 [(12 2± 2 2 )细胞 /HPFvs (2 9 5± 1 8)细胞 /HPF和 (1 4± 0 6 )细胞 /HPFvs (4 3± 0 8)细胞 /HPF ,P <0 0 1]。维甲酸治疗组肾脏TGFβ- 1mRNA表达显著低于对照组 (P <0 0 1)。 结论 :维甲酸能抑制大鼠UUO模型肾间质肌成纤维细胞局部增生和积聚 ,从而抑制肾间质纤维化。
AIM: To investigate the effect of retinoic acid on proliferation of renal interstitial myofibroblasts in a rat model of the left unilateral ureteal obstruction (UUO). METHODS: UUO model was established by unilateral ligation of ureter in 36 SD rats. Rats were divided into 2 groups: Retinoic acid-treated group and control group, each with 18 rats. UUO rats were treated with either daily subcutaneous injection of 10 mg/kg body weight of all trans-retinoic acid or vehicle alone two days before the operation until being sacrificed. Groups of 6 rats were killed on day 3, 7 and 12 after ligation of the left ureter. The percentage of renal tubular lesion, interstitial fibrosis score, the number of interstitial myofibroblasts, the number of proliferating myofibroblasts and the expression of TGFβ-1 mRNA were determined. RESULTS: There were significant accumulation and local proliferation of myofibroblasts in the interstitium of the UUO rats. On day 7 of the UUO model, the percentage of tubular lesions and interstitial fibrosis score were significantly lower in the retinoic acid-treated group than those in control group [(15.9±2.0)% vs (27.3±2.2)% and (0.47±0.12) vs (1.65±0.18), P<0.01]. The numbers of interstitial myofibroblasts and proliferating myofibroblasts in the retinoic acid-treated group were significantly lower than those in the control group [(12.2±2.2) cells/HPF vs (29.5±1.8) cells/HPF and (1.4±0.6) cells/HPF vs (4.3±0.8) cells/HPF, P<0.01]. Furthermore, the expression of TGFβ-1 mRNA was significantly lower in the retinoic acid-treated group than that of the control group (P<0.01). CONCLUSION: Retinoic acid suppresses interstitial fibrosis in a rat UUO model by inhibiting the accumulation and local proliferation of myofibroblasts in the renal interstitium.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2004年第5期809-814,共6页
Chinese Journal of Pathophysiology
基金
教育部高等学校全国优秀博士学位论文作者专项资金资助(199945)
广东省科委自然科学基金资助(990075)
广东省科委重点科研基金资助(99B06705G)
广东省教育厅"千
百
十工程"人才基金资助(Q校02011)
