| "Chinese herbs nephropathy" was said by European physician because of some herbs containing Aristolochic acid(AA) such as Caulis Aristolochiane Manshuriensis and Tetrandra Root may cause the renal damage in patients, although it have been used in China for thousands of years and be thought of safety. The clinic and animal studies were reported in the different magazine that lead to refuse more than ten Chinese herbs using in clinic by FDA of United Stats, MCA of England and Belgian government etc, so Caulis Aristolochiane Manshuriensis has been used to evaluate its nephrotoxicity in this study. Part 1. The relationship between nephrotoxicity of Caulis Aristolochiane Manshuriensis and time-dose course.Objective: to study the changes of renal function and morphrology on nephrotoxicity with different time and dosage.Methods: Sixty female Sprague-Dawley rats were randomly divided into 4 groups. Group A, B, C (n =16) andcontrol group D (n=12). The rats in group A, B, C were fed 2ml Caulis Aristolochiane Manshuriens with dosage of 1g.kg-1.d-1, 2g.kg-1.d-1and 4g.kg-1.d-1; Group D were fed with equal water. Rats take food and water freely in experimental period. After 12 weeks the animal without treatment were kept for 2 weeks. 24h urine were taken by metabolic cages and the blood from caudal vein at the end of week 6, 12, 14 was used to examine renal function, the kidneys were harvested on the last day for morphology and TNF study. Result: (1) In low-dose group(group A),there was no change on renal function and morphology compared with control group after 3 months, it shows that Caulis Aristolochiane Manshuriensis has no nephrotoxicity at limited dosage. (2) In medium-dose group(group B),the urinaryβ2-MG increased compared with control group(p<0.05). Light microscopy shows that there are partial vacuolation of renal tubule epithelial cells. When the drug was stopped, the β2-MG decreased and histomorphology became better than before. It shows that the renal damage by Caulis Aristolochiane Manshuriensis could be reversed in medium dosage. (3)In high-dose group(group c), protein, β2-MG, NAG,γ-GT in urine andβ2-MG in blood increased at the end of week6,12,14 compared with control group(P<0.05,P<0.01,P<0.05).Glucose in urine was increased. BUN , Cr in blood and TNF-α in renal tissue had the same change at the end of week 12 compared withcontrol group(P<0.05). Light microscopy shows that there are vacuolation, granular degeneration , necrosis in renal tubule epithelial cells at the end of week 6 and getting worse at the end of week 12. Electron microscope shows that there were the degeneration , necrosis on the microvillus and edema in mitochondrion of proximal tubule cells. At the end of week 14, tubulointerstitial fibrosis was seen by light microscope. Conclusion: The nephrotoxicity of Caulis Aristolochiane Manshuriensis was relevent with time-dose.Part 2 : Nephrotoxicity of Caulis Aristolochiane Manshuriensis Reduced by compouned formula cooperationObjective: To observe the changes of function and morphology by compouned formula cooperation, and the AA content in decotions.Method: ⑴,Study of nephrotoxicity in Gentian Liver-Purging Decoction(Long dan xie gan wan), Fire-Inducing Powder(dao chi san) and Caulis Aristolochiane Manshuriensis Decoction : 30 SD rats were randomly divided into 4 groups: Groups A(Caulis Aristolochiane Manshuriensis Decoction, n=8), B(Gentian Liver-Purging Decoction, n=8), C(Fire-Inducing Power, n=8), control group was D(n= 6). The rats of group A, B, C were fed with 2ml decotion which contain Caulis Aristolochiane Manshuriens at the dose of 4g.kg-1.d-1. Group D were fed with equal water.Rats took food and water freely during this period. Blood was taken from caudal vein and 24h urine got by Metabolic cage at the end of week 12 to examine renal function, the kidneys were harvested on the last day for morphology and TNF study. ⑵,Determine AA in decoctions by high performance liquid chromatograpy(HPLC): Caulis Aristolochi... |
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