Berberine protects diabetic nephropathy rats by inhibiting endoplasmic reticulum stress

Objective: The aim of this study was to investigate the effects of Berberine (BBR) on Endoplasmic Reticulum Stress (ERS) in renal tissue of Diabetic Nephropathy (DN). Methods: The DN RAT model was induced by high glucose and high fat diet combined with intraperitoneal injection of Streptozocin. The experiment was divided into 3 groups: normal group (NC group), model group (DN group) and berberine intervention group (DN + BBR group)(n = 6) . DN + BBR group was treated with 200 mg/kg/d on the basis of the model of DN. NC group and DN group were treated with the same dose of sodium carboxymethyl cellulose. After 6 weeks treatment measured various indicators (include body weight, renal index (KI = kidney weight/body weight), fasting blood glucose (FBG), blood creatinine (SCR), urea nitrogen (BUN) and 24h urine protein (24h Pro)). The pathological changes of kidney were observed by HE, PAS and Masson staining. The changes of glomerulus and renal interstitium were observed by transmission electron microscope. The expression of PERK, IRE1, ATF6, CHOP and Caspase3 were detected by immunohistochemical staining. Results: (1) SCR, Bun, FBG and 24hUpro in DN group were significantly higher than those in NC group and the renal function of DN group severely impaired. Compare with DN group the renal function of DN + BBR group was significant improved. There were significant differences in SCR, Bun, FBG and 24hUpro in each group (p < 0.01) . (2) The results of HE, PAS and Masson staining showed that the glomerulus in DN group was more irregular and larger than that in NC group; the lumen of glomerulus became narrowed, diffuse mesangial matrix was increased and renal tubule was edematous. The glycogen deposits and collagen fibers in the renal interstitium were increased and inflammatory cells were infiltrated. After the berberine rescued, the glomerular condition of DN + BBR group was obviously improved; the edema of renal tubules was alleviated; the deposition of glycogen was decreased and the collagenous fibers accumulation is relatively reduced. (3) The results of transmission electron microscope showed that the podocytes of DN Group were irregular and a large number of podocytes fused and broken. The basement membrane was inhomogeneous and thickened. Whereas, the morphological function of podocyte of DN + BBR Group was improved. And the basement membrane was slightly thickened. (4) Immunohistochemistry shows that the expression of Chop, PERK, IRE1, ATF6 and Caspase3 in DN group was significantly increased and the DN + BBR group was contrarily. The difference of protein expression was statistically significant (p < 0.05). Conclusion: These findings provide insights into the BBR can significantly improve the structure and function of kidney in DN rats. The hypothesis is that BBR can suppress endoplasmic reticulum stress and reduce the apoptosis of kidney cells, thus prevent the progress of DN and protect the kidney tissue.