OBJECTIVE  To investigate the potential benefits of Rhubarb Coptis in ameliorating kidney injury in obese mice with type 2 diabetes mellitus, focusing on its mechanism of action through the ROS/TXNIP/NLRP3 pathway.

METHODS  Sixty SPF 6-week-old db/db mice were randomly divided into model group, metformin group(0.26 g·kg⁻¹) and high, middle and low dose groups of Rhubarb Coptis(9, 4.5, 2.25 g·kg⁻¹). Another 12 db/m mice of the same age were selected as blank group. The body weight and fasting blood glucose of mice were measured after 8 weeks of intervention. Then the mice were killed, the renal function was measured by biochemical analyzer, the pathological changes of renal tissue were observed by HE staining and Hexaamine silver staining, the content of ROS in renal tissue was determined by frozen section staining, the protein expression levels of TXNIP, NLRP3 and Caspase-1 in renal tissue were detected by Western blotting, the expression levels of TXNIP, NLRP3 and Caspase-1 mRNA in renal tissue were detected by qPCR, and the contents of IL-1β and IL-18 in renal tissue were detected by ELISA.

RESULTS  Compared with the blank group, the fasting blood glucose and body weight, 24 h urinary protein and blood urea nitrogen increased significantly(P<0.05), while the urinary creatinine content decreased significantly in the model group(P<0.05). The kidney morphology changed, the nucleated cells decreased and the basement membrane thickened in the model group. The expression levels of TXNIP, NLRP3, Caspase-1 mRNA and protein in the kidney tissue of the model group increased significantly(P<0.05). The contents of IL-1β and IL-18 increased significantly(P<0.05), mean fluorescence intensity of ROS was significantly higher(P<0.05). Compared with the model group, the blood glucose and body weight of mice in metformin group and high, middle dose groups of Rhubarb Coptis were significantly decreased(P<0.05), 24 h urinary protein and blood urea nitrogen were significantly decreased(P<0.05), and the content of urinary creatinine was significantly increased(P<0.05). Each administration group improved the pathological morphology of renal tissue in different degrees. The expression levels of TXNIP, NLRP3, Caspase-1 mRNA and protein in renal tissue of mice in high and middle dose groups were significantly decreased, and the contents of IL-1β and IL-18 were significantly decreased(P<0.05), the mean fluorescence intensity of ROS was reduced in all cases(P<0.05).

CONCLUSION  Rhubarb Coptis can significantly improve the renal tissue injury of type 2 diabetic mice, and its mechanism is to regulate the response of ROS/TXNIP/NLRP3 pathway in renal tissue and inhibit the inflammatory reaction in renal tissue.