| Background and purposeDiabetic nephropathy (DN) is a metabolic disorder caused by diabetic glomerulosclerosis, is a common microvascular complications, which can cause kidney damage and into renal insufficiency, leading to proteinuria, hematuria, hypertension and edema, but also increases the incidence of cardiovascular events and mortality, as a main factor for disability and the death. It also causes end-stage renal disease (ESRD), that is, it eventually has developed into renal failure. Census data shows the incidence of diabetes is about 1.01 percent in population. DN as a serious kidney complication of diabetes, its incidence in patients with diabetes is about 20 percent abroad, rang from 0.9 to 36 percent domestically. In the course of 10 to 20 years of diabetes patients, regardless of age, about 50% of the patients may suffer from DN. once damage to the kidneys in diabetes patients occurs, they often develop to renal failure. The patients with diabetic renal failure accounts for 30 percent in the United States. DN leading to end-stage renal disease is the third largest cause in other developed countries, second only to hypertension and nephritis. DN takes up a front rank in secondary glomerulonephritis in China. It has been one of the first worldwide problems which urgently demand some solution. Pathogenesis of DN is very complex. Majority of scholars believe that the occurrence of high blood sugar is a prerequisite for kidney damage, microcirculation disorder caused by hypertension is an important factor to accelerate the progress of the kidney disease. Other factors, such as high glomerular filtration, advanced glycation end products increase; sorbitol and protein pathway activation of kinase C in cell, and cytokine genes involved in susceptibility and so on are also considered to be some important factors in the deterioration of the kidney disease.Benazepril belonging to the angiotensin-converting enzyme inhibitor is accepted drug by Western medicine to improve kidney function in DN. Benazepril with the function of inhibiting rennin-angiotensin system reduces the formation of angiotensin II, dilates efferent arterial of glomerula, decrease glomerular capillary pressure so that to reduce protein filtration, inhibits proliferation of glomerular mesangial cell ; maintains the integrity of the glomerular basement membrane structure and function; improves insulin sensitivity to tissue and reduce insulin resistance, and has synergistic hypoglycemic effect with hypoglycemic drug.Traditional Chinese Medicine thinks DN as a group of syndromes thirst with loss of body weight,edema, cloudy urine. The mechanism of DN that its base roots on both weak in Qi and Yin, and its sign shows with stagnant blood and moist sputum. The principle of treatment is improving Qi to promoting diuresis, promoting blood circulation to removing blood stasis. Yi-shen-pai-zhuo Decoction contains these Chinese herbs, Rhubarb, Astragalus, Ephedra, Poria, Radix Paeoniae Rubra and Salvia. Traditional Chinese Medicine thinks that Rhubarb releases excessive turbid substances by way of enhancing faces excretion and weed through the old to bring forth the new. Astragalus strengthens spleen and benefiting vital qi and helps the motion of blood and qi to avoid retention of body fluid effectively; Ephedra and Poria, remove water by way of kidney and gastrointestinal tract to correct edema; Radix Paeoniae Rubra and Salvia promote blood circulation to dissipate blood stasis.Modern pharmacology studies have shown that the rhubarb anthraquinones compounds improve blood glucose and lipid metabolism, promote renal circulation, reduce the proteinuria; Astragalus as an immunosuppressant reduces the immune damage to glomerula and proteinuria caused by the increased permeability; Water Salvia extract Salvia polyphenol-acid suppresses release of endothelin (ET) to improve kidney function; Ephedra could inhibits production of free radicals. This decoction with these Chinese herbs would have a certain role in the treatment of DN theoretically.The aim of this study is to observe the protective effect of traditional Chinese medical herbs Yi-shen-pai-zhuo Decoction combining benazepril on renal function of diabetic nephropathy and analyze the relative mechanism in it.Methods214 patients with DN were divided into two group in stratified, random and controlled design. The combination therapy group were treated with traditional Chinese herbs Yi-shen-pai-zhuo Decoction combining benazepril and the western medicine group were treated with benazepril only. Both group were the same such as to diet regulation, movement treatment, education, decreasing blood glucose and treatment based on syndrome. The treatment course underwent 3 months. Moreover a normal control group was set up. They were observed the change of 24-hour urinary protein, serum creatinine (Scr), serum creatinine clearance rate(Ccr), blood urea nitrogen, plasma glucose(PG), transforming growth factor (TGF-β), IL-6 and NO before and after treatment of patients with DN and normal control group.SPSS11.5 software was used in data statistic. Data represents in (x|-)±s and was treated by ANOVA analysis and q test. P < 0.05 means difference with statistic significance.ResultsThe content of 24-hour urinary protein, serum creatinine (Scr) and BUN decreased and serum creatinine clearance rate (Ccr) increased in the combination therapy group (Yi-shen-pai-zhuo Decoction combining benazepril) and the single benazepril group (P<0.05 or P<0.01), while the above effects of the combination therapy group were higher than the single benazepril group (P<0.05 ) .The single benazepril group can decrease plasma glucose (P<0.05 ) , but has no effect on plasma lipid(P > 0.05). The combination therapy group can decrease plasma glucose, TG and TC (P<0.05) and increase HDL (P<0.01). The decrease of plasma glucose in the combination therapy group more obvious than in the single benazepril group (P<0.05) .The level of TGF-βand IL-6 in the patients with DN increase obviously following decrease of renal function as compared to the normal control group (P< 0.01 or P<0.05) . Both treatment groups all decease the level of TGF-βand IL-6 in patients with DN in different stage of renal insufficiency (P<0.05 or P<0.01) , but the decrease degree of TGF-βand IL-6 in the combination therapy group is higher than in the single benazepril group (P < 0.05 ) .The level of NO showed the tendency of decrease after increase ahead following the progress stage of renal insufficiency. The level of NO increased obviously during renal compensation stage and decompensation stage in the patients with DN as compared to the normal control group (P<0.01 or P<0.05), but the level of NO decreased obviously during stage of renal failure (P<0.05); Both treatment groups decrease the level of NO during renal compensation stage and decompensation stage in the patients with DN as respectively compared to one before treatment (P<0.05 or P<0.01) , however, the decreased degree of NO level in the combination therapy group was higher than the single benazepril group (P<0.05); The level of NO upregulated during renal failure stage in the patients with DN as compared to one before treatment in the two treatment groups (P<0.05 or P<0.01), but the upregulated degree of NO level in the combination therapy group was higher than the single benazepril group (P<0.05) and closed to the level of normal control group (P >0.05).ConclusionYi-shen-pai-zhuo Decoction combining benazepril could obviously improve decreased renal function, which is better than the single benazepril group. Their treatment effects is relative to the decreasing of plasma glucose,plasma lipid,TGF-β,IL-6 and the regulation of NO. |
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