| Objective:Through decomposed recipes of Zhilong Huoxue Tongyu Capsule,observeing the effect of blood pressure,secretion function of vascular endothelial cell,infammation reaction etc in renovascular hypertensive rats,studying the mechanism of decreasing blood pressure by the whole recipe group and decomposed recipes,and provide a theoretical basis for the method of supplementing qi,activating blood circulation and dredging collaterals.Methods:The 110 male SD rats were randomly divided into normal group(n=12),sham operation group(n=12),operation group(n=86),the operation group was ligated the left renal artery to build two kidney one-clip(2K1C)renovascular hypertensive rat model.Screening 60 successful model rats were randomly divided into model group,captopril group,decomposed recipe one group(invigorating qi group),decomposed recipe two group(activating blood and removing stasis group),decomposed recipe three group(wenjing tongluo group),whole recipe group,every group have 10 rats.They were given the drug corresponding to 1 times/day gavage,and the same volume of normal saline given to the normal group,sham operation group and model group.Applying artery pulse method to measure blood pressure in rats by baseline blood pressure,2 weeks after surgery,6 weeks after surgery,treatment of 2 weeks and 4 weeks.after 4 weeks,the rats were took the blood from abdominal aortic for prepareserum.Determination of serumnitricoxide(NO)concentration,serumC-reaction protein(CRP)concentration,ELISA method was used to determinate serum Angiotension II(Ang II),Endothelin-1(ET-1).Taking the thoracic aorta,one part was used to detect the expression of Angiotension II Type 1 Receptor(AT1R)by immunohistochemistry method;another part was used to HE staining and observation and measure media thickness though light microcopy.Results:1.Generally observing each group of rats,normal groupandsham operation groupof ratsin goodnutrition,clean andshinycoat color,eating normal,gentle,quick action.The coat color of model group rats gradually turned yellow,harden and tarnished,increased water intake amount,slim body and unresponsive.Decomposed recipe group three appeared inyellowcoat color after fed one week,irritability,the color of eyes conjunctiva of two rats turned red.Other groups gradually recovered shiny coat color after treatment,docile temperament.2.The impact of drugson blood pressureof renovascular hypertensive rat:(1)Preoperation blood pressure,values of blood pressure of each group rats showed no significant difference.(2)Blood pressure after two weeks and six weeks: bloodpressure of model group,captopril group,decomposed recipeonegroup,decomposed recipe twogroup,decomposed recipe three group and whole recipe group were significantly higher than before surgery,there are differences compared with sham operation group and normal group(P<0.05).(3)Blood pressure after two weeks drenched:the blood pressure of normal group,sham operation group and model group had no essential change,compared with before drenching,compared with model group,the blood pressure of captopril group,decomposed recipe onegroup,decomposed recipe twogroup and whole recipe group decreased(P<0.05),while difference between model group and decomposed recipe threegroup was no statistically significant.(4)Blood pressure after six weeks drenched: compared with two weeks drenched,the blood pressure of captopril group,decomposed recipe onegroup,decomposed recipe twogroup and whole recipe group continually decreased;Compared with model group,except decomposed recipe threegroup,the blood pressure of the rest drug intervention group decreased significantly(P<0.05);Compared with the captopril group,blood pressure of decomposed recipe onegroup,decomposed recipe two groupand decomposed recipe threegroup increased(P<0.05),and the difference compared with whole recipe group was not statistically significant;Indecomposed recipe group,the whole recipe group had the biggest drop in blood pressure,compared with other decomposed recipe group,the difference was statistically significant(P<0.05).3.The impact of drugs on activating blood substances and inflammatory substances of renovascular hypertensive rats:(1)Serum NO,CRP: the concentration of serum NO of sham operation group and normal group was significantly higher than other groups,serum CRP levels were significantly reduced(P<0.05);The concentration of serum CRP was significantly lower(P<0.05);Compared with model group,except decomposed recipe threegroup,the concentration of serum NO of other drug intervention groups increased,the concentration of serum CRP decreased significantly(P<0.05);Compared with the captopril group,except whole recipe group,the concentration of serum NO of decomposed recipe onegroup,decomposed recipe twogroup and decomposed recipe three group decreased significantly(P<0.05),the concentration of serum NO of decomposed recipe onegroup is much higher than decomposed recipe twogroup and decomposed recipe threegroup(P<0.05);Compared with the captopril group,the concentration of serum NO of decomposed recipe onegroup and whole recipe group decreased,the difference was not statistically significant;Among decomposed recipe groups,the concentration of serum CRP of decomposed recipe onegroup and whole recipe group was much lower than other groups(P<0.05),Compared with decomposed recipe twogroup,the concentration of serum CRP of decomposed recipe threegroup increased significantly(P<0.05).4.Effects of drugs on AT1 R expression in the thoracic aorta of renovascular hypertensive rats:From light microscopic study,AT1 R expression is small amout expression in the normal group and sham surgery group,and abundantly expressed in the model group,decomposed recipe three group;in the captopril group,decomposed recipe three group,decomposed recipe three group and whole recipe group,the AT1 R expression were increased;AT1R expression in the sham group and the normal group were significantly lower than the other six groups(P<0.05).Compared with the model group,in addition to the decomposed recipe three group was no statistical difference,the AT1 R positive expressionin the rest intervention group were reduced(P<0.05).Compared with the Captopril group,positive expression of AT1 R in the decomposed recipe one group and decomposed recipe two group were obvious decreased(P<0.05).For the purposes of decomposed recipe group,the positive expression of AT1 R inwhole group was significantly lower than othergroups(P<0.05),compared with decomposed recipe one group,the positive expression of AT1 R in the decomposed recipe two group and decomposed recipe three group were significantly higher(P<0.05).(5)Effectsof drugs in the thoracic aorta media of renovascular hypertensive rats:From light microscopic study,The normal group and the sham group medial smooth muscle cells(VSMC)was slender shuttle line,regular arrangement and nuclei were blue staining.thoracic aortic medial in the model group and the decomposed recipe three group were thickening,and VSMC irregular arrangement and nuclei was increased;thoracic aortic medial in the captopril group,decomposed recipe one group,decomposed recipe two group,the whole recipe group were slight thickening,VSMC were irregular and nuclei slightly increased.compared with the sham group and the normal group,the other groups were significantly thickened(P<0.05);Compared with model group,in addition to the decomposed recipe three group,the other drug intervention groups were significantly decreased(P<0.05);compared with the whole recipe group,the media thickness in the other decomposed recipe group were significantly increased(P<0.05)and with no statistical difference in the captopril group.the media thickness in the whole recipe group was decresed than its decomposed recipe group(P<0.05);compared with the decomposed recipe one group,decomposed recipe two group and decomposed recipe three group were increased(P<0.05);media thickness in the decomposed recipe two group was lower than the decomposed recipe three group(P<0.05).Conclusion:1.Zhilong Huoxue Tongyu Capsule and the decomposed recipe one group(invigorating qi group),decomposed recipe two group(activating blood and removing stasis group)can signifcantly decrease blood pressure in the renovascular hypertensive rats and have a good therapeuic effect.Anti-hypertensive effect was the whole recipe group>decomposed recipe one group>decomposed recipe two group,while the decomposed recipe three group can not decrease blood pressure.2.The antihypertensive mechanism of Zhilong Huoxue Tongyu Capsule and the decomposed recipe one group,decomposed recipe two group on renovascular hypertensive rats maybe through the following way:(1)Regulation vasoactive substances,enhance vasodilatory activity through increase the release of NO,and decrease vasoconstrictor activity through reduce the release of ET-1 to achieve the purpose of protection the function of endothelial cells.(2)Reduce generation of CRP and relieve inflammation to improve the function of Vascular endothelial cell.(3)By reducing the generation of Ang II,reducing its receptor's expression of AT1 R.(4)Reduce smooth muscle cell proliferation and hypertrophy and decrease thickness to inhibition vascular remodeling.3.ZhilongHuoxueTongyu Capsule have a synergistic effect in the treatment of renovascular hypertensive through supplementing qi,activating blood circulation and dredging collaterals. |
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