| ObjectiveTo observe the effect of Yinqi Granule on the changes of IFN-γ,IL-4,IL-6,Transforming growth factor-β1(TGF-β1)and T-cell immunoglobulin domain and mucin domain-1(TIM-1)in IgA nephropathy rats.To explore the renal protective effect and possible mechanism of the prescription on IgA nephropathy,and to provide scientific basis for further development and study of the prescription.Methods50 healthy male Sprague-Dauley rats were randomly divided into 5 groups:normal group(n=10),model group(n=10),benazepril group(n=10),Yinqi Granule high-dose group(n=10)and Yinqi Granule low-dose group(n=10).The rats in the normal group were fed with 4 ml/kg distilled water every other day for 8 weeks,0.9%sodium chloride solution was injected subcutaneously once a week for 9 weeks,and 0.9%sodium chloride solution 0.2ml/rat was injected intravenously at the end of 6th and 8th weeks.Bovine serum albumin(BSA)solution(400mg/kg,1ml/100g)was administered every other day for 6 weeks,and then subcutaneously injected with 0.5ml carbon tetrachloride solution(CCL4 0.1ml),once a week for 9 weeks,and in combination with the lipopolysaccharide(LPS)solution of 0.05mg/day,respectively,for two times at the 6th and 8th week.At the 11th week after the beginning of the experiment,the rats in the benazepril group were given benazepril hydrochloride 2.1mg/kg/d(1ml/0.1kg)intragastrically,Yinqi Granule low-dose group 5.985g/kg/d(1ml/0.1kg)and Yinqi Granule high-dose group 17.955g/kg/d(1ml/0.1kg).The rats in the normal group and the model group were given 4 ml/rat distilled water for 10 weeks.Observation index1.The general state of the rat.2.rat 24-hour urine protein in rats3.Liver and renal function in rats.4.Serum levels of IgA,IFN-γ,IL-4,and IL-6.5.Renal pathological changes and immunofluorescence in rats.6.The expressions of TGF-β1 and TIM-1 in rat kidney.Results1.Uring the experiment,one rat died in the Yinqi Granule low-dose group.2.In the whole experiment,rats in the normal group were in good condition,their weight increased obviously,the reaction was sensitive,the coat color was luster,and the second was normal.The rats in the model group showed different degrees of trichomes after 6 weeks of administration.After 2 weeks of drug intervention,the above performance of the rats in each drug administration group was gradually improved,and the symptoms of the model group were not obviously relieved.3.Compared with the model group,the 24-hour urinary protein quantity of rats in each drug administration group was lower than that in the model group(P<0.05),and the effect of the Yinqi Granule low-dose group was the most obvious.4.There was no difference in ALB,BUN,and Scr among the serum of the rats in each group(P>0.05).5.The serum NAG of the model group,the Yinqi Granule high-dose group and the Yinqi Granule low-dose group were higher than those in the normal group.And the difference was significant(P<0.05),but the Yinqi Granule high-dose group was higher than the model group.The serum β2-MG in the model group,the Yinqi Granule high-dose group were higher than those in the normal group,the benazepril group,the Yinqi Granule low-dose group with a statistical difference(P<0.05).The levels of serum al-MG in the normal group,the benazepril group,the Yinqi Granule high-dose group,and the Yinqi Granule low-dose group were lower than those in the model group(P<0.05).6.The levels of serum IgA in the normal group,the benazepril group,the Yinqi Granule high-dose group,and the Yinqi Granule low-dose group were all lower than those in the model group,and there was a statistically significant difference from the model group(P<0.05).7.There was no significant difference in serum IFN-y between the model group and the normal group(P>0.05).The serum IFN-y in the Yinqi Granule low-dose group was higher than that in the normal group and the model group with significant difference(P<0.05).The levels of serum IL-4 in the normal group,the benazepril group,the Yinqi Granule high-dose group and the Yinqi Granule low-dose group were lower than those in the model group,and there was a statistically significant difference compared with the model group(P<0.05).Serum levels of IL-6 in the model group were significantly higher than those in the normal group(P<0.05).There was no significant difference between the high-dose group and the normal group(P>0.05).8.Pathological observation of the kidney(light microscopy):The glomerular and tubular structures of the kidneys in the normal group were normal.In the model group,the glomerular glomeruli of the rat kidney were swollen and the volume increased.Different degrees of mesangial cells and capillary endothelial cell proliferation and tubulointerstitial fibrosis occurred.The benazepril group,the Yinqi Granule high-dose group,and the Yinqi Granule low-dose group had mesangial cell proliferation and increased mesangial matrix,but also tubular interstitial fibrosis,but they were all reduced compared with the model group.9.Immunofluorescence:There was no fluorescence response in the glomerular kidney of the normal group.The glomerulus in the model group showed lumps or granular green fluorescence and the fluorescence intensity(++)-(+++).In the administration group,green glomerular expression was observed in rat glomeruli,but the fluorescence intensity was lower(+)to(++)than the model group,but the immunofluorescence of IgA in the low-dose group was the weakest.10.The expression of TGF-βi and TIM-1 were positive in kidney tissue of rats in each group.The expression of TGF-βi and TIM-1 in kidney tissue of normal rats was small,and the TGF-βi in kidney tissues of rats in model group.The expression of TGF-βi and TIM-1 increased significantly.The expression of TGF-βi and TIM-1 in the renal tissue of the benazepril group,the Yinqi Granule high-dose group,and the Yinqi Granule low-dose group were significantly decreased,and the difference between the three groups was not obvious.Conclusion1.Yinqi Granule can effectively reduce 24-hour urinary protein in IgAN rats,it is suggested that Yinqi Granule have a better effect at low doses than at high doses.2.Yinqi granules can not reduce the serum NAG of IgAN rats,but have an elevation effect,and the higher the dose,the greater the effect of the increase.Low doses of the Yinqi Granule and the benazepril tablets can reduce serum β2-MG,while high doses of Yinqi Granule do not reduce it.Both Yinqi Granule and benazepril tablets can reduce serum al-MG in IgA nephropathy rats.3.Yinqi Granule can effectively reduce IgA levels in serum of IgAN rats and can significantly improve kidneys.Pathological and immunofluorescence delayed the progression of IgAN.4.The low dose of Yinqi Granule can increase the serum IFN-y content of IgAN rats,while the high dose was not obvious.Yinqi Granule can reduce serum IL-4 and IL-6 levels,but the effect of low dose of Yinqi Granule to reduce IL-6 is not obvious.It is suggested that abnormalities of these inflammatory factors are involved in the pathogenesis of IgAN.5.Yinqi Granules can down-regulate the expression of TGF-β1 and TIM-1 in IgAN rat kidney tissue,suggesting that the occurrence of IgAN is closely related to the increase of TGF-pi and TIM-1. |
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