ABSTRACT
Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.
ABSTRACT
Objective: To study the clinical efficacy and safety of Yishen Huashi Granule (YHG) combined with Tripterygium wilfordii polyglycosides tablet (TWP) in the treatment of diabetic kidney disease (DKD). Methods: A total of 92 DKD patients in the stage of III-IV were selected from the department of nephropathy of the Jiujiang Hospital of Chinese Medicine. These patients were randomly divided into the observation group (46 cases) and the control group(46 cases). The observation group was treated with conventional therapy combined with TWP, and the control group was treated with TWP combined with YHG based on conventional therapy, both groups were continuously treated for three months. The urinary microprotein, serum albumin, urea nitrogen, creatinine, triglyceride, total cholesterol, urine IgG4, and urinary retinol binding protein were detected before and after treatment. The TCM syndrome score was evaluated and recorded. Blood routine, liver function, cellular immunity were detected after treatment. The recurrence and metastasis events were followed up and recorded. Results: After treatment, the total effective rate of the control group and the treatment group were 73.91% and 86.96% respectively, and the difference between the two groups was statistically significant (P < 0.05). Moreover, the levels of urinary microprotein, urea nitrogen and creatinine were (178.65 ± 31.72) mmol/L, (7.63 ± 2.15) mmol/L and (85.68 ± 14.74) μmol/L, respectively, which were significantly lower in the treatment group when compared with control group (P < 0.05). After treatment, the levels of serum albumin, triglyceride, and total cholesterol in the treatment and control groups were significantly improved (P < 0.05). The serum albumin level in the treatment group was significantly higher than that in the control group (P < 0.05), and the TG and TC levels were significantly lower than that in the control group (P < 0.05). The urine IgG4, and urinary retinol binding protein in the observation group were significantly reduced than those in the control group (P < 0.05). The white blood cell, and CD4+ in the observation group were higher than those in the control group (P < 0.05). The AST, ALT, and CD8+ in the observation group were significantly reduced than those in the control group (P < 0.05). TCM syndrome score in the observation group were lower than that in the control group (P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion: YHG combined with TWP have the effect of increasing the efficacy and reducing the toxicity in the treatment of DKD.