科罗索酸抑制NLRP3炎症小体活性在糖尿病肾病中的保护作用OACSTPCD

The effects and mechanism of corosolic acid(CA)on renal injury were investigated using diabetic nephropathy(DN)mice model,which was established by intrabitoneal injection of streptozocin(STZ)and feeding high-fat diet.Animals were randomly divided into blank control and model groups,three CA groups with low,medium and high doses groups.Upon 8 weeks post-administration,24 h urine displacements were measured for each mice group.In addition,blood urea nitrogen(BUN),blood glucose and glycosylated serum protein(GSP)were detected by kit.More biochemical parameters were collected for kidney.Kidney indexes were calculated by extracting the left side of kidney tissue.Histopathological changes of kidney were monitored by HE and PAS staining.Collagen IV and fibronectin were quantified by immunohistochemistry.Nucleotide binding oligomerization domain-like receptor protein 3(NLRP3),collagen IV,fibronectin m RNA IL-18 and IL-1β expressions in renal tissues were detected by real-time PCR.As a result,all parameters including blood glucose,GSP,24 h urine displacement,BUN and renal index increased significantly in model group by comparison with the blank group.Regarding the comparison of the three CA dose groups with model group,all the above parameters decreased significantly in CA dose groups in a concentration-dependent manner.Moreover,CA administration group showed significant improvement for the pathological changes of DN mice kidney,as well as decrease of collagen IV,fibronectin and their m RNA expressions in kidney tissue.Further studies revealed that CA could reduce renal injury in DN mice by regulating NLRP3 activity and IL-18 and IL-1β levels.Overall,CA could not only significantly improve the biochemical parameters during the pathogenesis of DN mice,but also effectively relieve the histopathological changes of kidney.It is worth mentioning that IL-18 and IL-1β in DN mice were inhibited through the mechanism of regulating NLRP3 activity.