Abstract
This study was explored the renoprotective effect of Tongxinluo (a Traditional Chinese Medicine) on diabetic kidney disease and its underlying mechanism. The results revealed significant (p<0.05) up-regulation of the expression of Bcl-2 and down-regulation of NF-κB p-p65, ASC, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, Bax and the ratio of Bcl-2 and Bax in immortalized proximal tubular HK-2 cells cultured by hyperglycemia combined with hyperlipidemia. In db/db mice, Tongxinluo treatment substantially decreased the 24 hours albuminuria excretion rate and the urine albumin-creatinine ratios and renal morphologic abnormalities. Similarly, the levels of NF-κB p-p65, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, and the ratio of Bcl-2 and Bax were down-regulated by Tongxinluo treatment in the kidney samples of db/db mice (p<0.05). Taken together, according to the anti-pyroptosis and anti-apoptosis effect of Tongxinluo, it shows the potential to be effective for the treatment of diabetic kidney disease.
Highlights
Diabetic kidney disease is a leading cause of advanced kidney disease and a typical complication of diabetes (Anders et al, 2018)
H&E and periodic acid-Schiff (PAS) staining results demonstrated that mice exhibited elevated vacuolation of renal tubular epithelium and slight mesangial expansion (Figure 2A)
We found that the protein levels of NF-κB p-p65, NLRP3, ASC, caspase-1, cleaved gasdermin D (GSDMD), and IL-1β were substantially down-regulated in the Tongxinluo group relative to the high-palmitic acid (HGHP) group (Figure 5A to 5K)
Summary
Diabetic kidney disease is a leading cause of advanced kidney disease and a typical complication of diabetes (Anders et al, 2018). The development of clinical therapy and the pathogenesis for diabetic kidney disease have made significant progress, the progression of it still cannot be controlled. The discovery of a novel and effective treatment for diabetic kidney disease patients is required. The diabetic kidney disease is a progressive microvascular complication arising from diabetes that is mainly concentrated on the glomerulus. Tubulopathy is the prime promoter and critical therapeutic target of the diabetic kidney disease (Gilbert, 2017). Tubulopathy is not secondary to the glomerulus, instead, it’s early and original features change (Zeni et al, 2017). The rate of renal decline was found to be more correlated with the degree of tubular damage and interstitial fibrosis (Zeni et al 2017), thereby indicating that the renal tubular injury in the context of diabetes is hard to be ignored
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