Establishment Of Model Of Chronic Aristolochic Acid Nephropathy In Rats Induced By Aristolochia Manshuriensis Kom And Study On Its Pathogenesis

BACKGROUNDAristolochic acid (AA) belongs to nitrophenanthrene carboxylic acid compound. It consists mainly of AA I and AA II, which differs from AA I with the absence of a methoxy group. In the 60's of the 20th century animal experiments showed that AA had anticarcinogenic effects and could augment phagocytotic activity of leukocytes. With the further studies and clinical applications, people found that AA was a potent carcinogen and had some serious adverse effects especially nephrotoxicity, which usually happened after taking Chinese herbs containing AA such as Aristolochia manshuriensis Kom (guan mutong) and Aristolochia fangchi (guang fangji). In 1964, Wu songhan reported the first case of acute renal failure after taking large dose of mutong decoctum. Chronic progressive renal failure after taking slipping pills containing Aristolochia fangchi was firstly reported in 1993 by Belgians. Therefore they named the disease Chinese herbs nephropathy (CHN), which is obviously inappropriate. Domestic scholars suggested that Aristolochic acid nephropathy (AAN) should be a more plausible term. According to the clinical and pathological manifestations of AAN, we classified this disease into three forms: acute AAN, renal tubule functional disturbance AAN and chronic AAN (CAAN). The patients suffered from CAAN undergo progressive deterioration of renal function with chronic hypocellular renal interstitial fibrosis in pathology, which is almost irreversible. Hence CAAN is the most destructive form of AAN. So far the precise pathogenesis of CAAN is still unaware as well as the mature therapeutic program. Therefore it is essential to establish an animal model of CAAN so that related studies could be carried on. In recent two years there have been several successful animal models of CAAN induced by AA in Belgium and China. Nevertheless, CAAN usually took place in the patients due to Chinese herbs containing AA (Aristolochia manshuriensis Kom, Aristolochia fangchi, etc.) but not AA itself. So we decided to establish a rat model of...