The Experimental Research Of XQ To Prevent And Treatment The Early Diabetic Nephropathy

Objective: Diabetic nephropathy (DN) are the most comm- on microvascularcomplications of the diabetic, DN are the first cause of death in patients with type 1 diabetes. DN incidence may berelated to the factors such as hypertension, hyperglycem- ia, hyp-erlipemia The main pathological features of DN are me- sangiummesangial cell proliferation, accumulation of matrix, m- esangium broden or nodule formation, as well as tubular, glome- rular basement membrane thickening, followed by the glomeru- lar sclerosis, and finally develop into renal failure.At present, the accumulation of glomerular matrixand base- Ment membrane thickening was characterized by excessive ac- cumulation of extracellular matrix (ECM). Matrix metalloprote- inase -2 (MMP-2) are the major ECM-degrading enzyme.The p- rocess of MMP-2 expression related to the changes of diabetic nephropathy renal pathological, which to protect the renal func- tion and morphology of diabetic rats, to retard the process of (DN) glomerular fibrosis. It can be adjusted by the expression of MMP-2 activity in prevention and treatment early DN. The abn- ormal activation of Reninangiotensin system(rennin-angio-tens insystem, RAS) in the pathogenesis of diabetic nephropathy pl- ays an important role. Blocking the system has a protective ef- fect on diabetic neph ropathy Therefore inhibiting the generat- ion of angiotensinⅡand blocking the treatment of DN are one of the important measures.Diabetes belong to the scope of Traditional Chinese Medi- cine,its Characteristics are deficiency heat, the course a long time, more than injurying Yin-chun, while gas consumption, which led to Yin Deficiency. Chinese medicine does not have the name of DN,but judged from the symptoms, is the one of variable cards. The characteristics pathogenesis of early DN are both Qi and Yin deficiency,"Treatment of the criterion"cloud: thirsting and stool frenquency is lower- wasting(Neijing says kidney-wasting ) " DN will be included in the lower-wasting's area. But Yin deficiency is the base of lower-wasting's pathoge- nesis, Be filled with hot is the surface of it.XQ's function is yi qi yang yin,qing re huo xue,surface together base are treatmen- ted. The prescription has been applied for many years, and it has better efficacy. Therefore the application of XQ treatmenting DN are must have basic theory and clinical practice. This experiment the use of intraperitoneal injection of streptozotocin chain urine (STZ) to copy the methods of DM rat model. View XQ on blood glucose, blood lipids, renal function, 24-hour urinary albumin excretion rate, kidney pathomorphology, kidney weight / body weight values, plasma and renal tissue angiotensin II (AngII) content, as well as the renal tissue MMPs -2 (MMP-2) expression. Preliminary study of early prevention and treatment of this side of the mechanism of DN. Yi qi yang yin,Qing re huo xue law for the prevention and treatment of early DN to provide a scientific basis for the experiment.Methods: 46 healthy SD rats(male, weighing 180±20 g) Select-ed, fed normal diet 1 week. blood sugar and urine sugar was tes-ted to be negative. according to body weight rats were randomlydivided into normal group (10), model group (12 ), XQ group(12) ,benazepril group(12). In exclusion to the normal group, the other three groups were taken by intraperitoneal injection of streptozotocin chain urine left (STZ) diabetic model replication. We regarded the rats as the model rats whose blood sugar≥16.7mmol/L,urine glucose was masculine Normal group was injected a considerable volume of citric acid buffer. The third model, model group, benazepril group, XQ group were given tap water, benazepril4.3mg/kg,XQ administered 36mg/kg, once a day. Normal group is also given the same volume of tap water orally. During the experiment, each group of animals freely eating, drinking water. In the fi-rst eight weeks using metabolic cages to collect 24-hour urine,measured by radio im- munoassay urinary albumin, urinary albumin excretion rate cal- culation (urinary albumin excretion rate, UAER), and measured urinary creatinine(urinary creatinine,Ucr). In the eight over the weekend, eight hours of fasting, weighing, all animals were ex- ecuted femoral artery blood, separation of serum, using automa- tic biochemical analyzer Detect rats blood glucose (PG), total cholesterol (TC), triglycerides. Three ester (TG), blood urea nitrogen (BUN), creatinine (serum creatinine, Scr), calculated creatinine clearance rate (creatinine clearance, Ccr). Asepsis check renal, after stripping renal capsule weighing, calculating the index of kidney hypertrophy(kidney weight / bodyweight, KW / BW). After the left kidney fixed paraffin-embedded, cut into 4 thick slices line HE and PAS staining Light microscope to observe morphological changes of renal pathology. Right kidne- y longitudinal incision in the sagittal plane, the check part of right kidney tissue homogenate after centrifugation, the superna- tant prepared from renal tissue AngII content measured. Organi- ze home right kidney more than the initialfixed 4% formaldehy- de, conventional fixed, paraffin-embeddedsections of the reserv- e,READY immunohistochemistry MMP-2 glomerular and tubu- lar expression and pathological imageanalysis software used to conduct semi-quantitative analysis. Statistical treatment, all data are expressed by x±s, using One-way ANOVA,the applicati- on data achieve statistical software SPSS 11.0.Results: (1)The general situation and serum glucose: Modelof diabetic rats after slow growth in weight, hair color, blood glucose increased, compared with the normal group there issignificant difference(P <0.01), XQ group must have a hypoglycemic effect, compared with the model group has significantly difference(P <0.01), benazepril group had no significant hypoglycemic effects, compared with the model group had no significant difference (P> 0.05).(2)Lipids: Eight weekends, with the exception of the normal g- roup, the remaining lipids in each group did not significantly in- creased, compared with the normal group were not significantly different (P> 0.05), XQgroup should not reduce the TG and TC levels, compared with the model group no significant difference (P> 0.05), benazepril group of lipid-lowering effect is not obvi- ous compared with the model group had no significant differen- ce (P> 0.05), between the two groups showed no significant difference (P> 0.05).(3)Renal function: Model group, BUN, Scr, Ccr compared with the normal group no significant difference (P>0.05), benazepril group and XQ group should not lower the BUN, Scr, Ccr level, compared with the model group had no significant differences (P>0.05), between the two groups showed no significant differ- ence (P>0.05).(4)24h urinary albumin excretion rate: Eight weekends, the model group 24h urinary albumin excretion rate was significant- ly higher than normal group (P<0.01),XQ group and the benazepril group could reduce the 24h urinary albumin excreti- on rate, compared with the model group has significantly differ- ence (P> 0.05).(5)Kidney weight/body weight ratio: Model group,kidney weight / body weight ratio was significantly higher than normal group (P<0.01),XQ group and the benazepril group of kidney weight/ body weight ratio was significantly lower than model g- roup, compared with the model group has significant difference (P<0.01),between the two was no significant difference (P> 0.05). (6)Plasma and renal tissue AngII content: Model group in plasma and renal tissue AngII were all higher than normal group (P<0.01). Benazepril plasma and renal tissue AngII content was significantly lower than model group (P <0.01), XQ group renal tissue AngII content was significantly lower than model group( P <0.01) and plasma AngII content of less than model group(P <0.05), betweenthe two was no significan t difference (P> 0.05).(7)Pathomorphological observation of renal tissue: Model group can be seen under a light microscope glomerular volume increases, larger balloon was lobulated, glomerular capillary basement membrane thickening, mesangial cell proliferation, mesangial area widened, mesangial matrix PAS staining was strongly positive, renal tubular epithelial cell swelling degenera- tion. XQgroup and the benazepril group rat kidney tissue lesions such as glomerular basement membrane thickening and mesang- ial cell proliferation than the model group has markedly impro- ved, mesangial area positive for PAS staining material reduced significantly.(8)Renal tissues of MMP-2 immunohistochemical results: Di- abetic group compared with the control group, renal tissue MM P-2 expression was significantly lower in plasma and kidney AngII content increased (P<0.01), XQ group and the benazepril group expression compared with the model group significantly increase, there is statistical significance (P<0.01), XQ group and the benazepril group was not significant (P>0.05). Semiquantit- ative analysis revealed that: the model group for each slice in the area of positive staining in the glomerular perspective the to- tal area were significantly lower than the normal group (P <0.01), prompted XQ group and the benazepril group can incre- ase in diabetic rat glomerular, tubular and renal interstitial in MMP-2 expression, and XQ group and the benazepril group had no significant difference (P>0.05).Conclusions:1 XQ can improve the experimental diabetic rats ingeneral status and lower blood glucose in diabetic rats, reducing the discharge of urine protein, the protection of the kidney.2 Inhibition of early kidney hypertrophy and hyperfiltration, improve kidney morphology can also simultaneously increase the expression of MMP-2 and lower levels of angiotensin, a cer- tain extent, can improve diabetic kidney damage, delaying the process of renal fibrosis.3 XQ on rat model of diabetes intervention role and benaz- eprilis basically the same, at Jiangtang, improve lipid metabolis- msuperior to benazepril.