摘要
目的探讨不同浓度维甲酸对单侧输尿管梗阻(UUO)大鼠肾组织趋化因子表达及肾组织炎症反应的影响。方法 135只SD大鼠随机分为假手术组、UUO组和维甲酸治疗组,每组45只。假手术组行左输尿管游离,不结扎;UUO组和维甲酸治疗组行左侧输尿管结扎。维甲酸治疗组术后每天分别给予不同剂量(5、10、20mg/kg)全反式维甲酸(ATRA)皮下注射,假手术组和UUO组注射同体积二甲亚砜花生油溶剂。于术后第3、7、14天观察各组肾小管损害、肾间质炎性细胞浸润程度,免疫组化和RT-PCR法观察病变肾组织趋化因子RANTES、CCR5、MCP-1、MIP-1α和TGF-β1表达情况。结果假手术组大鼠肾组织无明显病理改变,肾组织RANTES、CCR5、MCP-1及MIP-1α无明显表达。随着梗阻时间延长,UUO组大鼠肾间质炎性细胞浸润和肾小管损害逐渐加重(P<0.05),肾组织趋化因子表达进行性增加(P<0.01)。与UUO组相比,维甲酸治疗组肾间质炎性细胞浸润和肾小管损害程度显著减轻(P<0.05),肾组织趋化因子表达显著降低(P<0.01),但不同剂量维甲酸治疗组肾组织趋化因子的表达无明显差异。结论维甲酸能减少UUO大鼠肾间质炎性细胞浸润,减轻肾小管损害,抑制趋化因子表达,从而减轻肾脏炎症反应和纤维化。
Objective To investigate the effect of retinoic acid （RA） on chemokines and inflammation in kidney of UUO rats. Methods One hundred and thirty five healthy male SD rats were randomly divided into 3 groups （45 each）：sham operation group,UUO group and RA treatment UUO group. Left ureters of the rats were ligated in both UUO and RA treatment group,while in sham group the ureters were isolated only without further manipulation. Each group was divided into 3 subgroups （15 each）. Three RA subgroups were treated with daily subcutaneous injection of RA in a dose of 5,10 and 20mg/kg,respectively. The subgroups of the sham operation and UUO rats received same volume of dimethyl salfoxide and arachis oil. Five rats of each subgroup were sacrificed to get the kidneys on day 3,7 and 14 after operation. The area of renal tubular lesion and interstitial inflammation,and expression of chemokine were determined. The expressions of RANTES,CCR5,MCP-1,MIP-1α and TGF-β1 in kidney were assayed by immunohistochemistry and RT-PCR methods. Results No significant pathological change and expression of chemokine （RNTES,CCR5,MCP-1,MIP-1α） were detected in the renal tissues of sham operation group. Rats in UUO group showed progressive tubular cell damage,interstitial inflammation and fibrosis. Interstitial infiltration of macrophages and lymphocytes were found （P0.05）,and the protein content and mRNA expression of chemokine increased since the 3rd day up to 14th day （P0.01）. The interstitial inflammation and tubular lesion of RA group rats were dramatically reduced as compared with that in UUO group （P0.05）,and the protein and mRNA expression of chemokine were significantly decreased compared with those in UUO group （P0.01）. However,no significant difference in renal histology and chemokine expression was found among animals receiving different RA dosages. Conclusion RA may reduce renal interstitial inflammation and tubular lesion in UUO rats by down-regulating the expression of RANTES,CCR5,MCP-1 and MIP-1
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2010年第6期651-655,共5页
Medical Journal of Chinese People's Liberation Army
关键词
维甲酸
输尿管梗阻
炎症
纤维化
tretinoin
ureteral obstruction
inflammation
fibrosis
