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Zhenganxifeng Tang Essential Hypertension Vascular Reconstruction Caused Pathological Changes In Brain Tissue

Posted on:2008-10-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y H MengFull Text:PDF
GTID:1114360218456801Subject:Chinese medical science
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Objective: To provide the scientific basis of Zhengan Xifeng decoction on essential hypertension and following impairment, we observed the effects of Zhengan Xifeng decoction on morphological alternations of brain in spontaneously hypertensive rats (SHR) and the effects of serum containing metabolic ingredients of Zhengan Xifeng decoction on the injury of Human umbilical vein endothelial cells (HUVECs) and the proliferation of human umbilical artery smooth muscle cells (HUASMCs) stimulated by angiotensinⅡ(AngⅡ) and explored the mechanism of Zhengan Xifeng decoction on the injury of brain and vascular remolding due to essential hypertension.Methods: Thirty-two male SHR (fourteen-week-old) were divided into four groups at random: SHR group, high dose Zhengan Xifeng decoction group, low dose Zhengan Xifeng decoction group, enalapril group, compared with eight congeneric male Wistar-Kyoto rats (WKY). After eight weeks, the systolic blood pressure was measured by sixteen leads physiologic record system. The morphological alternations of brain were observed with HE. The concentrations of AnglI and ET-1 in plasma and brain were detected by radioimmunoassay. The expression of peroxisome proliferator-activated receptorγ(PPARγ) mRNA in brain was detected by the means of reverse transcription polymerase chain reaction (RT-PCR).The serum containing metabolic ingredients of Zhengan Xifeng decoction was taken from rats. HUVECs were cultured in vitro by collagenase digestive method. HUVECs were stimulated with 10-6mol/L AngⅡfor twenty four hours. The morphology and density of HUVECs were observed with invert microscope. The rate of apoptosis of HUVECs was analysed by the method of flow cytometry. The content of tumor necrosis factor-alpha (TNF-α) in supernatant medium was detected with enzyme-linked immunoadsorbent assay. The expression of PPARγmRNA in HUVECs was detected by the means of RT-PCR. HUASMCs were cultured by tissue explant method. HUASMCs were stimulated with 10-6mol/L AngⅡfor twenty four hours. The proliferation of HUASMCs was observed by MTT assay. The expression of osteopontin (OPN) mRNA was detected by the means of RT-PCR.Results: Compared with WKY group, the systolic blood pressure of SHR elevated significantly (P<0.05) and the brain of SHR had the ischemic and vascular remolding manifestation. High or low dose Zhengan Xifeng decoction could decrease systolic blood pressure of SHR significantly, but systolic blood pressure didn't get the normal level. High or low dose Zhengan Xifeng decoction could improve the pathological changes significantly. Compared with WKY group, the concentrations of AngⅡin plasma and brain and ET-1 in brain of SHR increased significantly (P<0.05). High or low dose Zhengan Xifeng decoction could decrease the concentrations of AngⅡin plasma and ET-1 in brain of SHR significantly (P<0.05). Compared with WKY group, the expression of PPARγmRNA in brain of SHR decreased significantly (P<0.05). High or low dose Zhengan Xifeng decoction could increase the expression of PPARγmRNA in brain of SHR significantly (P<0.05).10-6mol/L AngⅡcould increase the rate of apoptosis and the secrection of TNF-α, decrease expression of PPARγmRNA in HUVECs (P<0.05). The serum containing metabolic ingredients of Zhengan Xifeng decoction could decrease the rate of apoptosis and the secretion of TNF-αin HUVECs, increase the expression of PPARγmRNA (P<0.05). 10-6mol/L AngⅡcould elevate A490 and increase the expression of OPN mRNA in HUASMCs (P<0.05). The serum containing metabolic ingredients of Zhengan Xifeng decoction could reduce A490 and decrease the expression of OPN mRNA in HUASMCs(P<0.05).Conclusion: Zhengan Xifeng decoction decreases the systolic blood pressure and improves the pathological changes and vascular remolding in brain of SHR significantly.①Zhengan Xifeng decoction could increase the expression of PPARγmRNA, decrease the releasion of TNF-αand the rate of apoptosis to protect vascular endothelial cells.②Zhengan Xifeng decoction could inhibit the expression of OPN mRNA and the prolifertion of vascular smooth muscle cells.③Zhengan Xifeng decoction could increase the expression of PPARγmRNA and decrease the concentration of ET-1 and AngⅡto improve vascular remolding and protect the brain.
Keywords/Search Tags:vascular remolding, angiotensin II, endothelin-1, peroxisome proliferator-activated receptorγ, osteopontin, @Zhengan Xifeng decoction
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