| Part one:Qinguanjiangya Decoction in the treatment of primary grade 1 hypertension randomized crossover controlled trialObjective:To evaluate the clinical efficacy of Qingxuanjiangya Decoction treatment on patients of grade 1 hypertension.Methods:A randomized controlled clinical trial was conducted.According to the guidelines of Chinese hypertension 2010,80 cases of new high blood cases were included.They were divided into two groups by the random digital table method,including group A and group B.Group A and group B received Qingxuanjiangya Decoction(QXJYD)and lifestyle intervention for 4 weeks in the first stage respectively.After 4 weeks,group A and the group B cross converted to the general lifestyle intervention and the QXJYD for 4 weeks respectively.They measured their blood pressure in the morning and afternoon,and filled blood pressure records and symptoms at home.We collected the blood samples at 4th and 8th respectively,which were further used to detect the levels of Ang Ⅱ,TNF-α ET-1,CRP,Smad3 in surem.Results:QXJYD treatment significantly reduced blood pressure in patients with new grade 1 hypertension,the systolic blood pressure(SBP)decreased by 13 mmHg and the diastolic blood pressure decreased(DBP)by 9.1 mmHg on the 4th week after medication.In the afternoon,SBP and DBP decreased by 6.2 mmHg and 4.5 mmHg.After 4 weeks of follow-up,blood pressure was maintained well without serious adverse effects.No significant interference was found in the serum levels of Ang Ⅱ and ET-1 after QXJYD treatment.The level of TNF-a was significantly lower in group B,while no significant change was found in group A;the level of CRP in group A was significantly decreased,while no significant change was seen in group B,the level of Smad3 was the opposite.Conclusion:QXJYD treatment significantly reduces the new grade 1 hypertension patients with SBP and DBP,4 weeks after QXJYD withdrawal,maintain good blood pressure.QXJYD has the potential to improve the inflammatory state of hypertension.Part two:Pharmacodynamic mechanism of QXJYD on blood pressure regulation in spontaneously hypertensive ratsObjective:To investigate QXJYD on blood pressure in spontaneously hypertensive rats(SHR)and its effect on the activation of TGF-β1/Smad signal pathway in spontaneously hypertensive rats(SHR).Methods:SHRs were randomly divided into the control group(SHR-control)and the QXJYD group(SHR-QXJYD),which were administrated with QXJYD or equal volume of ddwater for 8 weeks;the Wistar-Kyoto rats were set as mormal control and were administrated with equal volume of ddwater for 8 weeks.Blood pressure,including SBP and DBP were monitered weekly.At the end of administration,blood samples were collected through abdominal aorta and tissues of thoracic aorta were collected for further determination.①HE staining,optical microscope combined with Leica Q Win V3 pathological image analysis system were used to determine the thickness(media thickness,MT),which indicates the effect of QXJYD on vascular remodeling;② ELISA and other biochemical kits were performed to detect Ang Ⅱ,ET-1 levels and RPA activity.③IHC,Q-PCR and Western blot were used to detect the effects of anti-glare and blood pressure-reducing decoction on expression of different types of collagen(Ⅰ,Ⅲ),PCNA,as well as activation of TGF-βsignal transduction pathway.Results:The blood pressure of SHR was higher than that in WKY control group(P<0.05),which were reduced after QXJYD,including SBP,DBP and MBP.Moreover,QXJYD treatment had no effect on the weight of SHR.The levels of Ang II,ET-1 and the activity of RPA in the serum of SHR were significantly reduced compared with the SHR-control group.Compared with WKY group,the membrane in aorta of SHR group was significantly thicker(P<0.05),vascular smooth muscle cells(VSMCs)were disordered,the number of cells in unit area was obviously increased,and in some cases,there was a phenomenon of intimal injury and inflammatory cell infiltration.Elastic membrane arrangement is disordered,loose,uneven and even broken;the results showed that the membrane thickness of the thoracic aorta was significantly improved,the pathological changes of aorta were improved.The levels of collagen(Ⅰ,Ⅲ),PCNA were decreased and TGF-β signal transduction pathways was inhibited by QXJYD in arterial.Conclusion:QXJYD could inhibit the increase of blood pressure in SHR rats,and improve the vascular remodeling induced by hypertension.By decreasing the levels of Ang II,ET-1 and the activity level of RPA in serum,as well as the expression of PCNA and activation of TGF-β signal transduction pathway in thoracic aortic smooth muscle cells might be one of the mechanisms of QXJYD on treatment of hypertension. |