| Background:End-stage renal disease (ESRD) has become a threat to human health of the global public health problem, which is the last stage of the chronic kidney disease. The primary glomerular disease is one of the leading causes of chronic kidney disease, its persistent proteinuria lead to kidney damage, relatively independent risk factor for progression, and it is the important reason for renal pathological changes. Therefore controlling proteinuria, improving renal function, to a great extent, can reduce renal fibrosis, delay the progress of chronic kidney disease. Renal fibrosis is caused by abnormal accumulation of extracellular matrix, renal tubular function and the loss of renal interstitial capillary, which due to a variety of long-term effects of all kinds of kidney disease.The main pathological manifestations are glomerular sclerosis and renal interstitial fibrosis. Kidney mesangial cells are one of the major effector cells of the extracellular matrix, and play an important role on regulating the synthesis and degradation of extracellular matrix. In pathological conditions, such as mesangial proliferative IgA nephropathy, with lupus nephritis, diabetic nephropathy, and some other immune mediated glomerular diseases, in which the main characteristics of mesangial cell damage performance are the proliferation of mesangial cells and extracellular matrix. Thus, reducing excessive proliferation of mesangial cells, restraining the generation of extracellular matrix, promoting the degradation of extracellular matrix, is of great significance to reduce glomerular damage, prevent the progress of kidney disease, and delay the renal fibrosis. Increased synthesis of extracellular matrix, reduced degradation, including the the disordering of extracellular matrix degradation system is the main factor to result in renal fibrosis. In recent years, studies have shown that regulating the balance of extracellular matrix degradation system can relieve inflammation of kidney tissue reaction and the degree of pathology.Modified Hangqichifeng Decoction (MHD)is a proved recipe, summed up by tutor, professor zhang yu, from years of clinical experience on the treatment of proteinuria in chronic kidney disease (CKD) first or second period; Preliminary experimental studies obtain, the drug-containing serum-MHD can reduce the proliferation of mesangial cells in mice induced by LPS, decline mesangial extracellular matrix in the expression of FN, LN, Col IV; At the same time it can increase Bax, Caspase 3 expression, reduce the Bcl-2 expression and the Bcl-2/Bax ratio, promote the role of mesangial cell apoptosis. The section of clinical observation, observing the clinical efficacy and safety of MHD in treating patients with albuminuria of 1-2 period of chronic kidney disease (CKD).The section of experiment research, studying the MHD on mice mesangial extracellular matrix degradation induced by LPS, and the influence of alpha-SMA, to provide further experimental and theoretical basis for the clinical application of the MHD.1. Clinical observation:Objective:To observe the clinical efficacy and safety of MHD in treating patients with albuminuria of 1-2 period of chronic kidney disease.Methods:The cases of single randomized controlled design, each case study is divided into three rounds, each round 2 period, namely the period of treatment and control period, each 4 weeks, according to the random Numbers of each round table was a randomized, decided to treatment, on the basis of the conventional foundation treatment, treatment period use MHD, treatment with controlled benazepril, curative effect for patients with clinical symptoms integral and 24 hours urinary protein, quantitative safety index for liver and kidney function, electrocardiogram (ecg), etc. Record laboratory indexes before and after the experiment of patients.Results:MHD can significantly improve the spleen and kidney deficiency and blood stasis in patients with clinical symptoms and improve its patients electrocardiogram (ecg) in liver and kidney function in patients with and without adverse effects. Conclusion:MHD can significantly improve the spleen and kidney defi ciency and blood stasis in patients with clinical symptoms and significantly reduce the proteinuria; And it had no adverse effect on liver and kidney function and electrocardiogram (ecg), protective effect on kidney function to a certain degree.2. The experiment research:Objective:To reseach the effects of MHD on mice induced by LPS glomerular mesangial cells matrix degradation and alpha SMA protein expression.Methods:Respectively with high, medium and low doses of MHD, telmisartan, pure water for irrigation of rat stomach after three days, the preparation of drug-containing serum and ck in serum, using 10 pecent of each group containing medicine serum DMEM culture, in vitro culture of GMCs, LPS as stimulating factor. Cells can be divided into the control group (blank serum group), model group (LPS), telmisartan group. MHD high dose group, middle dose group, low dose group.1. Using the method of ELISA detection on mesangial cells supernatant of MMP-1 and TIMP-9, Col Ⅳ content; 2. Using Western Blot method to observe of GMCs MMP-2 and TIMP-2, PAI-1, alpha SMA protein expression.Results:(1) Compared with the normal group, model group Col Ⅳ content increased significantly, p<0.01, significant difference between two groups; Compared with model group, flavored astragalus root soup red wind high, middle dose group and telmisartan group can obviously reduce the extracellular matrix in the Col Ⅳ protein expression, traditional Chinese medicine (TCM) there was no significant difference between low dose group and model group;(2)Model group compared with normal group.MMP-9/TIMP-1 MMP-2/TIMP-2 proportion reduced, the two groups had significant difference; Compared with model group, telmisartan group,Chinese medicine high, medium and low dose group, MMP-9/TIMP-1,MMP-2/TIMP-2 ratio was increased, the telmisartan group, Chinese medicine rise in larger ratio of high, middle dose group compared with model group significant difference (p<0.01):Low dose group compared with model group, the ratio is slightly raised, but there was no statistically significant difference between the groups. Telmisartan, MHD high, medium and low dose group can adjust drug serum induced by LPS, MMP-9/TIMP-1,MMP-2/TIMP-2 imbalance, and Chinese medicine high dose, telmisartan group rise in dose effect is superior to traditional Chinese medicine, Chinese medicine low dose group. (3) Compared with the normal group, model group the expression of PAI-1 significantly increased (p<0.01); Compared with model group, telmisartan group of PAI-1 protein expression decreased significantly, the significant difference between groups (p< 0.05), high, middle dose group of Chinese medicine. PAI-1 expression were significantly lower, very significant difference, p<0.01; Low dose group compared with model group, expression of PAI-1, significant difference, p<0.05). Traditional Chinese medicine (TCM) protein expression PAI-1 high dose group was obviously less than in the traditional Chinese medicine (TCM) dose group, telmisartan group, low dose group. Telmisartan group compared with the traditional Chinese medicine low dose group, p>0.05, there was no significant differences in the two groups. (4) Compared with the normal group, model group of alpha SMA expression increased significantly, p<0.01; High dose group compared with model group, p<0.01, a very significant difference; Telmisartan group, Chinese medicine dose group compared with model group, the expression of alpha SMA significantly decreased, p<0.05, significant differences; Low dose group compared with model group, p>0.05, there was no statistically significant difference. High dose group compared with the traditional Chinese medicine low dose group, p<0.05, they had significant differences.Conclusion:MHD can adjust the ECM degradation disorder induced by LPS, hike, MMP-9/TIMP-1,MMP-2/TIMP-2 ratio,inhibition of ECM in the Col Ⅳ overproduce, promote the degradation of ECM, reduce the accumulation of ECM, cut alpha SMA protein expression, and a certain amount of activity relationship. |
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