| Aim: In this paper,the effects of Qingda Granule(QDG)on blood pressure and myocardial fatty acid ? oxidation in spontaneously hypertensive rats(SHR)were studied by animal experiments.The protective mechanism of QDG on hypertensive heart injury was discussed from PPAR-?/PGC-1? signaling pathway.To further elaborate the mechanism of QDG in the treatment of hypertension,and providing further experimental basis for clinical treatment of hypertension and protection of heart.Methods: The Wistar and SHRs of 6-week-old SPF males were selected as the subjects,6 in each group.They were randomly divided into WKY group,SHR group,SHR+QDG(0.4g/kg)group and SHR+QDG(0.8g/kg)group.One week after adaptive feeding,WKY group and SHR group were given saline 1 ml/day,SHR+QDG(0.4g/kg)group was given 0.4g/kg/day,and SHR+QDG(0.8g/kg)group was given 0.8g/kg/day.Blood pressure was measured every week.After 12 weeks,heart tissues were collected.Heart pathological changes were observed by HE,fatty acid content in myocardium was detected by GC-MS,gene expression of ANP and BNP related to myocardial hypertrophy was detected by Q-PCR,protein expression of CPT-1,CPT-2,LCAD,MCAD,PPAR-? and PGC-1? were detected by IHC.Results: 1.Blood pressure measurements showed that the systolic blood pressure of SHR was significantly inhibited after administration of QDG 2 weeks,and the diastolic blood pressure and mean blood pressure of SHR were significantly inhibited after administration 3 weeks.2.HE staining results showed that cardiac myocytes in WKY group were orderly arranged,homogeneous cytoplasmic staining,no degeneration and necrosis of cardiac myocytes;cardiac myocytes in SHR group were obviously hypertrophic and myocardial fibers were disordered;after administration of QDG,the pathological changes of cardiac myocardium in rats were improved.3.Q-PCR results showed that QDG could effectively down-regulate the levels of ANP and BNP in myocardial tissue.4.The results of GC-GC showed that the content of linoleic acid and arachidonic acid decreased in SHR group,and the content of linoleic acid and arachidonic acid increased significantly after administration of QDG;the content of palmitic acid and stearic acid increased in SHR group,and the content of palmitic acid and stearic acid decreased significantly after administration of QDG.5.IHC results showed that the protein expressions of CPT-1,CPT-2,LCAD and MCAD in SHR group were significantly down-regulated compared with WKY group.After administration of QDG,the protein expressions of CPT-1,CPT-2,LCAD and MCAD were significantly up-regulated.6.IHC results showed that the expression of PPAR-?/PGC-1? signaling pathway was significantly down-regulated in SHR group compared with WKY group.After administration,the expression of PPAR-?/PGC-1? was significantly up-regulated..Conclusion: 1.QDG can inhibit the increase of SHR blood pressure and effectively improve the physical and morphological changes of SHR heart.2.QDG can down-regulate the content of palmitic acid and stearic acid in SHR myocardium,up-regulate the content of linoleic acid and arachidonic acid in myocardium,thus promoting the level of fatty acid ? oxidation in myocardium.3.QDG can enhance fatty acid ? oxidation in myocardium by up-regulating the expression of CPT-1,CPT-2,LCAD and MCAD,which are key enzymes of fatty acid ? oxidation.4.QDG may improve the level of fatty acid ? oxidation in SHR myocardial cells by activating PPAR-?/PGC-1? signaling pathway and play a protective role in the heart. |
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