| With the increase of incidence of Type 2 Diabetes Mellitus (T2DM), Diabetic Nephropathy (DN) has become the important cause of end-stage renal disease. Therefore,prevention and treatment of DN and delay the onset of DN as well as its development is imminent. This paper make a comprehensive overview about clinical and basic research on both Chinese and Western medicine of DN in recent years. It also summarized academic thoughts and clinical experience of professor liu in treating of DN. On the basis of previous studies, this paper evaluated clinical effect of Gu shen jiang bai granules on the treatment of DN through before and after self-controlled trials; By spontaneous obese db/db mice, discussed the mechanism and key points of Gu shen jiang bai granules in treating DN.Objective:Evaluate clinical efficacy of Gu shen jiang bai granules to the treatment of early DN patients with patterns of spleen-kidney deficiency and dampness-heat and blood stasis.Observe the influence of Gu shen jiang bai granules acted on TGF-β1-Smad signaling pathways in obese db/db mice, clarify its mechanism for the treatment of DN.Materials and Methods:Adopt prospective self-controlled trials, carrying on a 12-week clinical effect observation and safety evaluation on early DN patients by choosing 36 cases of spleen-kidney deficiency and dampness-heat and blood stasis, those who take antidiabetics or use insulin treatment with FBG <7.8/L, 2-hour PBG≤11.1/L, HbA1C<8.5%; meanwhile,taking antihypertensive drugs, with blood pressure≤140/90 mmHg.32 db/db mice,divided into four groups which are model group,group of irbesartan,goup of Gu shen jiang bai granules and group of both Gu shen jiang bai granules and irbesartan. Set up 8 db/m mice as normal group, giving medicine through administration by gavage for 12 weeks, observing the changes of blood glucose and body weight every week, as well as the 24 h urine protein quantitative every 4 weeks. After the trial, make the detection of serum insulin and glucose, creatinine and urea nitrogen; Meanwhile,detective SOD, MDA content of renal tissue. Make ues of HE staining, Masson staining and PAS staining, TUNEL apoptosis in renal pathological observation; Take Immunohistochemistry method to detect kidney TGF-beta 1, α-SMA and E- Cadherin protein expression. Western blot method to detect kidney TGF-β1、 BMP7、 a-SMA protein expression. And RT-PCR method to detect kidney TGFβ1R、 Smad3 genetic expression。Results:Among 36 cases of patients with T2DM, 3 cases fell off, 3 eliminated, and 30 patients completed the 12-week clinical observation. Results found that Gu shen jiang bai granules can significantly reduce the excretion rate of 24 h urine trace albumin (p<0.01),with the total effective rate 86.7%; and remarkably improve gradings of TCM syndromes(p<0.01), with the total effective rate 76.7%, in which notably improved the symptom of soreness and weakness of waist and knees(p<0.01), urine turbidity symptoms (p<0.01),and the symptom of weary and fatigue (p<0.01).While the points of symptoms such as dry thirsty mouth, tastes bitter and night urinary got mild decreased. Under treatment, Gu shen jiang bai granules had no effect to liver and the kidney, and no obvious adverse reaction occurred.After 12 weeks of treatment, Gu shen jiang bai granules can significantly reduce 24 h urinary albumin in obese db/db mice (p<0.05), and increase renal tissue SOD content(p<0.01), decreasing renal tissue MDA content (p<0.01), while have no effect on kidney weight/body weight ratio, blood glucose,insulin,Cre.ALT. HE staning prompted gu shen jiang bai particles can alleviate kidney pathological changes, Masson staining hinted Gu shen jiang bai granules can significantly reduce the collagen area ratio(p<0.01); PAS staining illustrated that Gu shen jiang bai granules can notably reduce glycogen area ratio (p<0.01); Tunel results suggested that Gu shen jiang bai granules can remarkblely reduce the apoptosis average optical density value (p<0.01);Immunohistochemistry results suggested that Gu shen jiang bai granules can significantly reduce the TGF-β1 (p<0.05), a-SMA (p<0.01) protein expression levels,and increase the E-cadherin (p<0.05) protein expression levels. Result of Western blot suggests that Gu shen jiang bai granules can significantly reduce the TGF-β1 protein expression (p<0.01) and a-SMA (p<0.01) protein expression, while mild increase BMP7 protein expression Result of RT-PCR suggests that Gu shen jiang bai granules can significantly reduce the TGF-β1R (p<0.05) Smad3 (p<0.01) genetic expression. The overall detection index of group Gu shen jiang bai granules is close to group of irbesartan,some index of curative effect is superior to western medicine, and part of the detection index of group of both Gu shen jiang bai granules and irbesartan is better than that of a group of drug alone.Conclusions:1.Gu shen jiang bai granules can significantly reduce 24 h urine trace albumin of patients of spleen-kidney deficiency and dampness-heat and blood stasis on early DN,and improve clinical symptoms.2.Gu shen jiang bai granules can reduce urinary albumin in obese db/db mice,protect kidney function and delay the renal damage3.Resistance to oxidative stress is one of the mechanism in renal protection of Gu shen jiang bai granules. TGF-β1 a-SMA, BMP-7 、 E-cadherin signaling pathway are key points which Gu shen jiang bai granules directed at for the treatment of DN.4.Gu shen jiang bai granules combined with ARB antihypertensives have a synergistic effect. |
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