| Objective:Investigate the effects of modified zexie decoction on the blood pressure,renal function and the regulation effect of AngⅡ-N ADPH-ROS pathway in the salt-sensitive hypertensive rats.Explore the antihypertensive mechanisms of modified zexie decoction salt sensitive hypertension.Methods:60 male DS rats were randomly divided into 6 groups,with 10 rats in each group.In addition to the normal control group,which eat the normal food,the other five groups were given 8%NaCl high salt purified feed,feed them for 4 weeks.After 4 weeks,start the drug intervention.The control group and model group were given distilled water,valsartan group received valsartan 7.2 mg/(kg·d)gavage,low dose of Chinese medicine group 5.4 g/(kg·d)gavage,Chinese medicine middle dose group 10.8 g/(kg·d)gavage.Chinese Medicine high dose group 21.6 g/(kg·d)gavage,which lasts for 4 weeks.The blood pressure,body weight and urine volume were measured before and after treatment,and urine,serum,kidney tissue and the kidneys to body weight radios of rats were measured 4 weeks later.Test the content of related indexes of renal function serum BUN,Scr,Na+,K+,Cl-,β 2-MG,24hALb.Detect the mRNA expression of ATR1,NOX4,p22 and p47 in rats’ AngⅡ-NADPH-ROS pathway factors by RT-PCR,test protein expression with the Western blot at the same time.Results:1 High salt diet can lead to hypertension,and the model of salt-sensitive hypertensive rats is successfully replicated.2 Compared the blood pressure with the model group,and Chinese medicine group(p<0.01 or p<0.05),there was significant difference,with statistical significance.3 Compared with the model group,the serum BUN level in low dose of Chinese medicine group(p<0.05),with statistical significance.Compared with the model group,the level of Na+decreases and the level of K+ elevates in the serum of Chinese medicine group(p<0.05),with statistical significance.There was a significant difference between the five groups with high salt diet in both kidneys weight and the model group the kidneys to body weight radios(p<0.01),was statistically significant.Compared with the model group,the 24 hALb、NAG in the urine of the Chinese medicine group(p<0.01 or p<0.05),with remarkable difference and statistical significance.4 The morphological changes of renal tissue were visible,HE staining:increased glomerular volume was not obvious in the traditional Chinese medicine group.There was only mild mesangial proliferation,deep staining substance decreasing,most tubular capillary cavities opening,renal tubule in good shape,and were continuous,compared with the model group.PAS staining:the reduction of glomerular volume in Chinese medicine group was small,the PAS positive substance decreased,and the thickening of glomerular basement membrane were alleviated.Transmission electron microscopy:The Chinese medicine groups showed the segmental thickening of small amount of basement membrane,but the membrane structure was continuous.Foot process is normal.There was no obvious hyperplasia mesangial cells and matrix.Intracellular organelle structure was better than that in the model group.Mitochondria were swollen,but cristae structure exists.Some of the renal tubules showed increasing lysosome in the cytoplasm,and there was no obvious abnormality in the rest part.5 Tested the gene and protein expression level of AT1R,NOX4,p22 and p47 using Real Time PCR and Western blot.The experiment showed the mRNA and protein expression of AT1R,NOX4,p22 and p47 in model group DS rats’ kindey were all remarkable higher than the normal control group(p<0.01).Both the valsartan and modified zexie decoction can decrease the mRNA and protein expression of AT1R,NOX4,p22 and p47(p<0.05 or p<0.01),which has a significant difference and statistical significance,compared with the model group.Compared the Chinese medicine group and the valsartan group among the variant target gene between the treatment group and model group,the AT 1 R in Chinese medicine groups(p<0.01),with remarkable difference;the NOX4 in Chinese medicine middle dose and high dose group(p>0.05),with no difference,and is similar to valsartan;p22 and p47 in Chinese medicine middle dose group(p>0.05),with no difference,and was similar to valsartan.Compared the target protein in the Chinese medicine groups and the valsartan group,AT1R in Chinese medicine middle dose group(p>0.05),p22 and p47 in Chinese medicine low dose and midlle dose group(p>0.05),NOX4 in Chinese medicine groups(p>0.05),with no remarkable difference.The effect of Chinese medicine group is similar to the valsartan groupConclusion:1 High salt diet can lead to hypertension,modified zexie decoction can reduce the blood pressure caused by high salt diet.2 Modified zexie decoction can improve the renal function of rats,and have the diuretic effect.It can improve the pathological morphology of rat kidney tissue,have the effect of draining water,eliminating stasis and resolving phlegm3 Modified zexie decoction can regulate the mRNA and protein expression of AT1R,NOX4,p22 and p47 in AngⅡ-NADPH-ROS pathway,have the effect of draining water,eliminating stasis and resolving phlegm.Thus have the effect of reducing blood pressure and protecting renal function. |
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