RESUMO
The aim of the present study was to investigate whether modified Huangqi Chifeng decoction (MHCD) could be an effective treatment against Doxorubicin-induced nephrosis in rats and whether it regulates autophagy via the phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway. A total of 40 male Sprague-Dawley rats were randomly divided into blank, model, telmisartan and MHCD groups. The rat model of nephrosis was induced by intragastric administration of Doxorubicin for 8 weeks. Rats were housed in metabolic cages and urine was collected once every 2 weeks to measure 24-h protein levels. Blood samples were obtained from the abdominal aorta and levels of albumin (ALB), total cholesterol (TCH), triacylglyceride (TG) and serum creatinine (Scr) were assessed. Renal pathological changes were examined using hematoxylin-eosin, Masson's trichome and periodic acid-Schiff staining. Podocytes and autophagosomes were observed using an electron microscope. The expression and distribution of microtubule-associated proteins 1A/1B light chain 3B (LC3), LC3-I, LC3-II, beclin-1, PI3K and mTOR were determined using immunohistochemistry and western blotting. At weeks 6 and 8, 24-h proteinuria significantly decreased in the MHCD group compared with the model group (P<0.05). Compared with the model group, the MHCD group exhibited significantly reduced levels of TG, TCH and Scr, as well as significantly increased ALB levels (P<0.05). MHCD was demonstrated to prevent glomerular and podocyte injury. The number of autophagosomes was significantly decreased and the expression of beclin-1, LC3, LC3-I and LC3-II was inhibited following MHCD treatment compared with the model group (P<0.05). MHCD treatment significantly increased the expression of PI3K and mTOR in Doxorubicin nephrotic rats compared with the model group (P<0.05). In conclusion, MHCD was demonstrated to ameliorate proteinuria and protect against glomerular and podocyte injury by inhibiting excessive autophagy via the PI3K/mTOR signaling pathway.
RESUMO
BACKGROUND: To evaluate the efficacy and safety of Danggui Buxue Decoction for renal anemia when combined with western medicine treatment of anemia. METHODS: Electronic searching Medline, Embase, Web of Science, Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), WanFang data, Chinese Sci-tech periodical full-text database (VIP). Randomized controlled trials reported results of efficacy and safety of Danggui Buxue Decoction in combination with western medicine treatment of anemia for renal anemia. The "risk of bias assessment tool (Version 5.1.0)" of Cochrane Handbook was applied to assess the quality of included trials and RevMan 5.3 software was used for data analysis. RESULTS: A total of 111 studies was retrieved, seven studies including 460 cases were included, the methodological quality of included trials was poor. The result of meta-analysis demonstrated that there was no difference in hemoglobin (Hb) [weighted mean differences (WMD) =-8.75, 95% confidence interval (CI): (-18.64, 1.13), P=0.08], whereas the subgroup analysis showed the difference was significant when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5:1 [WMD =-16.27, 95% CI: (-28.73, -3.80), P=0.01], increase of Hb was more effective in experimental group than control group and the difference was not significant when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5≠1 [WMD =-0.57, 95% CI: (-4.52, 3.39), P=0.78]. There were significant differences in red blood cell (RBC) [WMD =-0.49, 95% CI: (-0.69, -0.28), P<0.00001], hematocrit (HCT) [WMD =-1.92, 95% CI: (-3.15, -0.69), P=0.002] and clinical efficacy [odd ratio (OR) =0.30, 95% CI: (0.13, 0.69), P=0.004] between Danggui Buxue Decoction combination group and control group, the experimental group was better than control group. There was no adverse event reported in the experimental group. CONCLUSIONS: Danggui Buxue Decoction in combination with conventional western medicine (CWM) for renal anemia might be superior to CWM alone and there was no adverse event in the experimental group, it might be more effective when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5:1. However, the quality of included studies was not high, and less attention was paid to the safety, high quality randomized controlled trials are needed to further confirm the findings.
