摘要
目的:观察关木通所含马兜铃酸(AA)不同时间致大鼠肾损害及川芎嗪、泼尼松和贝那普利的干预作用。方法:将雄性SD大鼠随机分为六组,每组24只。正常组(C组)予蒸馏水3ml/d灌胃,模型组(M组)、泼尼松组(P组)、贝那普利组(B组)、川芎嗪Ⅰ组(LⅠ组)和川芎嗪Ⅱ组(LⅡ组)均予关木通水煎剂(含生药2g/ml、AA0.54mg/ml、AAⅠ0.46mg/ml)5g/(kg·d)灌胃。2h后C组与M组予NS,其余四组分别予泼尼松5mg、贝那普利1.7mg、川芎嗪各50mg、150mg/(kg·d)灌胃。120天和180天后检测肾功能及血常规,并观察组织病理和超微病理。120天时每组处死7只,180天时处死剩余大鼠。结果:随着时间的延长,大鼠血肌酐与血尿素氮及尿NAG与24h尿蛋白定量逐渐升高,而血红蛋白(Hb)与红细胞比容(HCT)逐渐降低。M组与C组比差异非常显著(P<0.001);其余四组与M组比较差异显著(P<0.05),其中P组和LⅡ组降低或升高尤为明显。C组为正常肾组织表现。M组光镜:120天可见肾小管上皮细胞片状空泡变性、肿胀,以近髓部小管病变较显著,刷状缘消失,大部分肾小管基膜(TBM)裸露和(或)断裂,部分肾间质有轻度灶性炎细胞浸润和部分肾小球可见轻度节段硬化;180天病变加重,小管上皮细胞呈大片状空泡变性,以皮质部小管病变较明显,部分小管萎缩,大部分肾间质有胶原纤维增生。电?
Objective: Chinese herb medications containing aristolochic acid (AA) have been reported as sociated with acute and chronic interstitial nephritis in different clinical set tings. In this study, we established a rat model by administering with caulis ar istolochiae manshuriensis(CAM) containing AA. And with this model, we investigat ed the histological changes of AA nephropathy at different stages, and observed the effect of agents as ligustrazine(L), prednisone(P) and benazepril(B), in the intervention of AA nephropathy. Methodology:Male SD rats were divided into six groups (24 rats in each group) at random, th e normal control group (C group, 3ml of distilled water given by gavage per day) , the treatment control group (M group), (L group), prednisone treatment group (P group) and benazepril treatment group (B group), ligustrazine treatment grou p-1 (L-1 group )and ligustrazine treatment group-2 ( L-2 group). Rats in M group and other treatment groups was administered by gavage with 5 g/(kg·d) CA M decoction (CAM 2 g/ml, AA 0.54 mg/ml, AAⅠ 0.46 mg/ml). After 2 hours in terval, normal saline was given in M group, prednisone was given at 5 mg/(kg· d) in P group, benazepril was given at 1.7 mg/(kg·d) in B group, ligustrazin e at 50 mg/(kg·d) in L-1 group, and ligustrazine at 150 mg/(kg·d) in L-2 group by gavage respectively. 24 hours urine samples and blood samples were ta ken at the 120 th days and the 180 th day. Seven rats randomly chosen in each group were sacrificed at the 120 th day, with the others sacrific ed at the 180 th day. Renal function and blood routine were examined. Rena l tissue were processed for histopathology of light microscopy and electronic mi croscopy. Results:As compared to the C group, the mean serum creatinine(SCr), blood urea nitrogen (BUN), urinary β -N-acetyglocosamidose(NAG) and 24 hour urinary protein excre tion(UPE) increased, and the mean level of hemoglobin and hematocrit decreased as the observation time increased in all the treatment groups and treatment cont rol group. Significant differences in mean SCr were found between the treatment control group and all the treatment groups (P group vs. M group, L1 group vs. M group, L2 group vs. M group: P value <0.001; B group vs. M group, P value <0.005). Among the treatment groups, significant differenc e of mean SCr, BUN, NAG and UPE were found, with the lowest levels in the L2 gro up, followed by the L1 group, and the P group, and the highest in the B group. Rats in the M group sacrificed at the 120 th day developed segmental glomer ulosclerosis and various tubulointerstitial lesion including interstitial cellul ar infiltration, brush border loss, denuded tubular basement membrane, patchy v acuolar changes and swelling in tubular epithelium, especially in the proximal tubule. Rats in the M group sacrificed at the 180 th day developed more sev ere non-cellular tubulointerstitial changes including severe patchy vacuolar ch anges of tubular epithelium (especially in the cortex area), massive interstitia l fibrosis without cellular infiltration. Electronic microscopy showed rats in the M group sacrificed at the 120 th day developed vacuolar changes and nec rosis of proximal convoluted tubular epithelium, karyopyknosis, mitochondria sw elling, disarranged ridge beam, increased lysosome and segmental glomeruloscler osis. Rats in the M group sacrificed at the 180 th day developed fatty dege neration of proximal convoluted epithelium, TBM thickness, fibroblast prolifera tion, collagen fiber deposition in the interstitium, segmental glomerular baseme nt membrane thickness. While rats in the four treatment groups developed less s evere tubulointerstitial changes, especially in the P group and the L2 group. Conclusion:Rats administered with CAM containing AA developed acute tubulointerstitial lesi on in the early stage(before 120 days of observation), and chronic non-cellular tubulointerstitium fibrosis during the later stage (after 180 days observation period). Agents as ligustrazine, prednisone and benazepril, showed protective ef fects in t
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2005年第2期105-109,共5页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
上海市科学技术发展基金资助项目(NO:20034060)
中国博士后科学基金资助项目(NO:2004035666)
