Therapeutic mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii polyglycosides in the treatment of Henoch-Sch?nlein purpura nephritis rats based on PERK/eIF2α pathway
Objective:To explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii glycosides(GTW)in improving endothelial damage in Henoch-Schonlein purpura nephritis(HSPN).Methods:A total of 72 rats were randomly divided into a blank control group and a modeling group.The modeling group was used to construct an HSPN rat model.After successful modeling,the rats were randomly divided into a model group,a Qingre Zhixue Formula group,a GTW group,a combination group,and a prednisone group.The blank control group and model group were given physiological saline by gavage,while the other treatment groups were given corresponding drugs by gavage twice a day.After 4 weeks of intervention,the 24-hour urine total protein quantification of rats was measured;the PAS staining of rat kidney tissue under light microscope was observed;the deposition of IgA in the glomerulus of rat kidney tissue under fluorescence microscopy was observed;ELISA for detecting serum expression of IL-1β,TNF-α,VCAM-1 and VEGF;the protein expression of p-PERK,p-eIF2α,GRP78 in rat kidney tissue were detected by Western Blot.Results:Compared with the blank control group,the total protein content in the urine in 24 h of the model group rats was significantly increased(P＜0.05),in the model group,glomerular mesangial hyperplasia was observed,with narrowing of the glomerular capillary lumen due to compression,accompanied by a small amount of inflammatory cell infiltration,and there were clustered green fluorescence with high intensity in the glomerular mesangial area of rats,the expression of IL-1β,TNF-α,VCAM-1 and VEGF significantly increased(P＜0.05),while the expression of p-PERK and p-eIF2 α,GRP78 protein significantly increased(P＜0.05).Compared with the model group,the combination group could significantly reduce the quantitative level of total urine protein in 24 h(P＜0.05),improve renal mesangial hyperplasia and IgA fluorescence deposition,and reduce serum IL-1β,TNF-α,VCAM-1 and VEGF(P＜0.05),reduce the expression of p-PERK and p-eIF2 α,GRP78 protein(P＜0.05).Conclusion:The combination of Qingre Zhixue Formula and GTW can effectively reduce the total protein level in urine of HSPN model rats,alleviate renal pathology and endothelial damage,and its mechanism may be related to the regulation of renal endoplasmic reticulum stress PERK/eIF2 α pathway.
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