Study On Each Prescription Compatibility Reduce Cinnabar-caused Nephrotoxicity In Wanshi Niuhuang Qingxin Pills

ObjectiveTo confirm on each prescription in Wanshi Niuhuang Qingxin Pills reduce nephrotoxicity in rats that caused by cinnabar,And provide reference for further study on the substance basis of compatibility attenuation of Wanshi Niuhuang Qingxin pills.MethodsA total of 168 healthy SD rats(180±20g),female and male were half and half,were randomly divided into 7 groups Rats were given by gavage cinnabar+each prescription(cinnabar+coptis,cinnabar+scutellaria,cinnabar+gardenia,cinnabar+turmeric,cinnabar+bezoar),establishment of cinnabar group and the whole recipe at the same time,containing 1.0g/kg cinnabar at all of the groups,once a day for 12 weeks.During the administration,the situation in rats such as behavior,appearance,body weight change,diet,secretion,excretion,etc,were observed.The rats were weighed twice a week,the dosage according to body weight adjustment.24 h urine were collected after repeated dosing 4,8,12 weeks and drug withdrawal for 4 weeks.The blood and kidney of 6 animals(3male and 3 female)in each group were collected under general anesthesia.The mercury contents in the blood,the kidney and the urine were determined by Zeeman atomic absorption mercury analyzer.The concentrations of blood uric acid and serum creatinine were measured by automatic biochemical analyzer.The content of hydroxyproline in renal tissue was tested by sample alkaline hydrolysis test kit.Kidney tissue slices were made,and pathological changes were observed under light microscope by HE staining and Masson staining.m RNA expression of TNF-? and IL-10 was tested by Real-time PCR.The data were represented by average and standard deviation,and were analyzed by SPSS17.0 statistical software.The difference among the groups was analyzed by single factor analysis of variance(One-Way ANOVA),and the the difference between two groups was analyzed with S-N-K or Dunnett's T3.The level of significance test was 0.05.ResultsDuring the study,the general conditions of rats were normal and their body weight was steadily grown,there was no significant difference between different groups.After repeated dosing 4,8,12 weeks and drug withdrawal for 4 weeks,The content of blood mercury of cinnabar and coptis,scutellaria,gardenia or turmeric compatibility group were lower than that of the single cinnabar group(P<0.05),blood mercury of each prescription group were higher than the whole recipe group(P<0.05).The content of kidney mercury in cinnabar and Coptis,gardenia or turmeric compatibility were lower than cinnabar group(P<0.05),each prescription were higher than the whole recipe,The content of urine mercury in cinnabar and Coptis or turmeric compatibility were lower than cinnabar group(P < 0.05),cinnabar and scutellaria,gardenia,turmeric or bezoar compatibility were higher than the whole recipe.After repeated dosing8,12 weeks and discontinuous drugs for 4 weeks,the content of BUA in cinnabar and scutellaria,gardenia,turmeric or bezoar compatibility were lower than cinnabar group(P < 0.05),the content of SCr in cinnabar and coptis,scutellaria,gardenia,turmeric or bezoar compatibility were lower than cinnabar group(P<0.05).Kidney was dark red(Chinese herbal pigment)in the whole recipe,cinnabar and gardenia compatibility,with the extension of time,thedeeper the color,a slight improvement after discontinuous drugs for 4 weeks.Under the light microscopy,the kidney tissue of cinnabar group rats was renal tubular epithelial cell vacuolar degeneration,swelling,bureaucratic narrow,part of the tubular structure disappeared,the gap widened,lumen protein tube,interstitial infiltration of inflammatory cells(lymphocytes and mononuclear cells),mild interstitial fibrous hyperplasia lesions,mainly at the junction of renal cortex pulp.The pathological lesions in the whole recipe,each prescription lighter than cinnabar group,there were pigment deposition in the whole recipe,cinnabar and gardenia compatibility.After repeated dosing 12 weeks,the expression of TNF-? and IL-10 in the whole recipe were lower than cinnabar group(P<0.05),the TNF-? expression of male rats in cinnabar and Coptis,turmeric compatibility were lower than cinnabar group(P<0.05),the TNF-? expression of female rats in cinnabar and scutellaria compatibility were lower than cinnabar group(P<0.05).ConclusionsWanshi Niuhuang Qingxin Pills reduce cinnabar-caused nephrotoxicity in rats.Cinnabar and coptis,gardenia or turmeric compatibility can antagonistic mercury absorption caused by cinnabar or promotes urinary mercury excretion;reduce the accumulation of mercury in renal tissue.Wanshi Niuhuang Qingxin Pills and each prescription can reduce the renal pathological changes caused by cinnabar.Wanshi Niuhuang Qingxin Pills antagonistic nephrotoxicity in rats that caused by cinnabar is more obvious than cinnabar and each prescription compatibility.