| Part ? Clinical studySection 1 study on TCM diagnosis and treatment of hypertension byusing Expert questionnairesurveyObjectiveTo investigate TCM diagnosis and treatment of hypertension and the theory of Vessel distention by using Expert questionnaire in the national,To summarize the knowledge of clinical experts on hypertension and the scientificity,rationality and practicability of the theory of Vessel distention.To provide clinical practice support for the development of the theory of Vessel distention,and to provide a clinical basis for the innovation of Chinese medicine diagnosis and treatment of hypertension and the development of Chinese and Western medicine experts in the diagnosis and treatment of hypertension.MethodsAn clinical expert questionnaire was designed with TCM diagnosis and treatment of hypertension,the expert is directly fill in the letter,and network survey.After the experts completed after the recovery,statistical treatment,the results of the survey database was established with Epidate software,SPSS 17.0 software was used for statistical analysis.Results(?)General situation1.There are total of 53 hospitals and 19 provinces involved in the investigation,collected number of 529 expert questionnaireswas,the number of 6 are lack of information,the recovery rate of 100%,the effective rate of 98.9%.2.Total of 523 experts surveyed,270 males and 253 females,the minimum age of 30 years old,the maximum age of 65 years old,mean age 40.55 + 7.77.218 are intermediate title physician,accounting for 41.7%of the total number of professors;176 are detupy senior physician doctors,33.6%of the total number;129 are senior physician,accounting for the total number of 24.7%.(?)Investigation on hypertension diagnosis and treatment of traditional Chinese Medicine1.Common symptoms of hypertension:Treatment of patients with hypertension symptoms besides common vertigo,headache,headache,there is also a mixed type(headache,headache and dizziness,etc.)and asymptomatic patients,the occurrence rate of asymptomatic patients is not uncommon2.Hypertension TCM disease name recognition:92.9%experts believe that vertigo can not be equated with hypertension;98.5%experts believe that the headache can not be equated with hypertension;87.2%think that wind dizziness can not be equated with hypertension;485(92.7%)experts agree and consider the adoption of the new right more suitable TCM disease name corresponding to hypertension in TCM diagnosis.3.Investigate the diseease location of hypertension in TCM:85.9%experts agree that in the blood vessel;66.5%experts agree that in five viscera;34.8%experts believe that in six lollow;each other agree that the disease is Chongren,Qingqiao collaterals,etc.4.TCM syndrome differentiation of hypertension:Number of 389(74.4%)experts use syndrome differentiation of viscera;number of 365(69.8%)experts using syndrome differentiation of blood vessel;number of 173(33.1%)experts use syndromes differentiation with eight principles;number of 93(17.8%)experts use syndrome differentiation of six meridians;number of 7(1.3%)experts use other syndromes differentiation.5.single TCM syndrome type of hypertension:single common syndromes of hypertension are hyperactivity of yang,turbid phlegm syndrome,blood stasis syndrome,yin deficiency syndrome,qi stagnation syndrome,heat syndrome,qi deficiency syndrome,yang deficiency syndrome,deficiency of the blood syndrome.6.complex TCM syndrome type of hypertension:investigated 11 kinds of complex TCM syndrome type of hypertension,showed that the Yin deficiency and yang hyperactivity syndrome,hyperactivity of liver Yang,phlegm and blood stasis,Phlegm turbidity obstruction syndrome,Liver kidney yin deficiency syndrome are the most common type.deficiency of Qi and blood syndrome,deficiency of yin and yangsyndrome are rare.(?)Investigation of "Vessel distention" theory1.nvestigation of clinical experts' familiarity with "Vessel distention" theory:523 experts,familiar with the "Vessel distention"theory is only 36(6.9%);understand the "Vessel distention" theory of 108 experts(20.7%);heard of "Vessel distention " theory expert 232(44.4%);not heard of "Vessel distention " theory expert 147(28.1%).2.To investigate the recognition of "Vessel distention" as the name of hypertension in Chinese Medicine:number of 459(87.8Y%)experts agree"Vessel distention" as a reasonable name of hypertension in TCM.and that the experts have unreasonable number of 64(12.2%)experts are disagree.Conclusions1.Combined with the investigation of common symptoms of hypertension,it shows that the name of traditional Chinese medicine for hypertension is unreasonable.2.Most experts believe that diseease location of hypertension at the blood vessels,use syndrome differentiation of blood vessels is reasonable.3.The single most common disease syndromes of hypertension are hyperactivity of yang,turbid phlegm syndrome,blood stasis syndrome,the most common compound syndromes are Yin deficiency and yang hyperactivity syndrome,hyperactivity of liver Yang,phlegm and blood stasis,phlegm,blood stasis is the basic pathological basis of hypertension.4.Most experts agree "Vessel distention" as a reasonable name of hypertension in TCM."Vessel distention" theory rationality has been recognized by experts.Section 2 Meta analysis on the treatment of hypertension with compound QiMa capsuleObjectiveMeta analysis was carried out through the clinical research on Compound QiMa capsule in the treatment of primary hypertension,to assess the efficacy and safety of Compound QiMa capsule in the treatment of primary hypertension,to provide a theoretical basis for Compound QiMa capsule in clinical application and promotion.MethodsRetrieval before January 30,2016 China National Knowledge infrastructure(CNKI),Wanfang Data and VIP information database(conferences,journals,Dissertations Database),included on Compound QiMa capsule hypertension,target organ protection,improving lipid metabolism and adverse reaction were reviewed.According to the inclusion and exclusion criteria were included in the literature on the literature.Analyzed with RevMan 5.3 software.The effect of the weighted mean difference(WMD)or odds ratio(OR)and its 95%confidence interval(95%CI).First the heterogeneity of the ? 2test,if not among studies(P?0.10,I2?50%),fixed effect model was used statistical if there is heterogeneity between studies;P<0.10,I2>50%),using a random effects model-subgroups of statistical effect;Z test was used to compare the effect of(assuming a =0.05 level test),results are listed in the forest plot.And the funnel plot analysis of publication bias.Result(?)Literature collection resultsAccording to the retrieval strategy,the literature was retrieved and the unqualified literature was removed.A total of 26 articles were included.All of the literatures were comparable to the hypothesis test.(?)Effect of treatment on overall clinical outcomeA total of 16 articles reporting the effect of Compound QiMa capsule total efficiency of treatment in patients with hypertension,Compound QiMa capsule alone or combined with western medicine treatment of 748 cases of the control group,the treatment of 631 cases of hypertensive patients.Compound QiMa capsule used alone or combined with western medicine in the treatment of hypertension patients after total effective rate than the control group significantly,the difference was statistically significant(P<0.01).(?)Effect on blood pressure1.Effect on systolic blood pressure:A total of 19 articles were reported on the effect of Compound QiMa capsule contraction pressure in patients with hypertension,Compound QiMa capsule alone or combined with western medicine treatment of 806 cases of the control group,the treatment of 720 cases of hypertensive patients.Compound QiMa capsule in the treatment of patients with hypertension after contraction pressure compared with the control group decreased significantly(P<0.05).2.Effects on diastolic blood pressure:A total of 19 literatures have reported the effect of Compound QiMa Capsule on diastolic blood pressure in hypertensive patients,the Compound QiMa capsule alone or combined with western medicine treatment of 806 cases in the treatment of 720 cases of patients with hypertension.Compound QiMa capsule after treatment of diastolic blood pressure in hypertensive patients than in the control group had no significant difference(P>0.05).(?)Influence of TCM syndrome integralA total of 13 literatures have reported the effect of Compound QiMa Capsule on patients with hypertension symptoms integral,Compound QiMa capsule alone or combined with western medicine treatment of 481 cases,control group treated 475 patients with hypertension.Compound QiMa capsule after treatment in patients with hypertension syndrome scores compared with the control group decreased significantly(P<0.01).(?)Side effectA total of 16 articles reporting on adverse reaction of Compound QiMa capsule treatment process,of which 2 articles reporting xerostomia,unspecified number of cases;5 reported 9 cases of patients with cough;1 reported diarrhea abdominal pain,an unspecified number of cases;8 reported in the study no adverse reaction in the process of.16 report,Compound QiMa capsule alone or combined with western medicine treatment of 520 cases,control group treated 503 patients with hypertension.Compound QiMa capsule after treatment in patients with hypertension the incidence of adverse reactions than the control group significantly decreased(P<0.05).Conclusions1.Compared with the control group,the compound capsule can significantly improve the overall clinical efficacy of the treatment of patients with hypertension.2.Compared with the control group,the compound capsule can significantly reduce the systolic blood pressure in patients with hypertension,but the effect of diastolic blood pressure is not obvious.3.Compared with the control group,the efficacy of the treatment of the patients with hypertension after the treatment of compound Shenqi capsule was significantly better than that of the control group.4.Compared with the control group,Compound QiMa capsule had cough or micro cough and other adverse reaction rate is low.Part ? Experiment researchExperiment ? The effect of Compound QiMa capsule on blood pressure and vasoactive factor expression in spontaneously hypertensive ratsObjectiveTo observe the effective of the compound of QiMa capsule on spontaneously hypertensive rats blood pressure,and vascular endothelial in NO,ET-1,Ang?,expression of ACE in serum,to investigate the effect of Compound QiMa Capsule on blood pressure and vasoactive substances in the RASS system,and provide a reliable basis for the clinical application of traditional Chinese Medicine in the field of hypertension.MethodsAfter 50 SHR rats feeding 1 weeks,the rats according to body weight were randomly divided into 5 groups:group SHR(distilled water,10ml/Kg/d),Irbesartan Capsules group(Irbesartan Capsules,13.5mg/Kg/d),Irbesartan Capsules + Compound QiMa capsule group(Irbesartan Capsules,13.5mg/Kg/d+Compound QiMa capsule,1.8576g/Kg/d)that compound QiMa capsule low dose group(Compound QiMa capsule,1.8576g/Kg/d)and Compound QiMa capsule high dose group(Compound QiMa capsule,9.288g/Kg/d),10 rats in each group,half male and half female.10 WKY rats as normal control group(distilled water,10ml/Kg/d)respectively.The Compound QiMa capsule and Irbesartan Capsules into a solution,by gavage once a day,all rats weighing once a week,and adjusted according to the changes of body mass dose,lasted for 16 weeks.The rats in the first before drug administration,after every 2 weeks using the United States CODA-2 rats were used to monitor blood pressure.After the experiment,the rats fasted 24 hours after weighing,with 10%chloral hydrate on rats by intraperitoneal anesthesia(0.3ml/100g),completely after anesthesia,rats were supine fixed on the table,disinfection of rat abdominal skin with 75%alcohol,quickly cut cut by peritoneal tissue,to expose the abdominal aorta,blood from the abdominal the aortic blood collection needle,blood mark into the centrifuge,at the speed of 3000rpm/min centrifugal centrifugal 10min,after carefully learn from the upper yellow transparent liquid(plasma),a marker of EP pipe,placed in the refrigerator to-70? and cryopreserved,measured the serum levels of SHR,with ELISA assay NO?ET-1?Ang??ACE?ACE2?Ang(1-7)content;blood after the end of the tissue scissors cut quickly open the chest,fully exposed the heart,the heart samples about 200mg into the EP tube,placed in the refrigerator frozen-70? to detect the level of pERKl/2 protein expression by Western Blot,real-time fluorescence quantitative PCR(qRT-PCR)detection the level of ACE?ACE2 and Mas mRNA;fully exposed and completely isolated carotid artery,remove tissue around blood vessels,cut blood vessels and placed in a pre cooled saline flush,cut about 1cm of the carotid artery in the Formaldehyde Solution fixed with pathological HE staining and immunohistochemistry,the remaining blood vessels into the EP tube.In-70? fridge frozen for subsequent use of detection.Result(?)The effect of compound QiMa Capsule on blood pressure of systolic blood pressure1.Before treatment,SHR group,irbesartan group,irbesartan + QiMa low dose group,low dose group and QiMa SBP of high dose group were higher than WKY group,the difference was statistically significant(P<0.01);group SHR,irbesartan group,irbesartan + QiMa low dose group,QiMa the low dose group,high dose group QiMa,comparing the 22 groups,no difference in SBP levels(P>0.05),comparable.2.After treatment of second weeks.The blood pressure of irbesartan group began to decrease,compared with QiMa low dose group,the difference was statistically significant(P<0.05);compared with SHR group,irbesartan group,irbesartan + QiMa low dose group,low dose group and QiMa high dose group SBP level had no significant change(P>0.05);after 4 weeks,6 weeks compared with SHR group,irbesartan group,irbesartan + QiMa low dose group,no significant changes of QiMa low dose group and high dose group QiMa SBP levels(P>0.05).After 8 weeks,10 weeks,12 weeks after the Irbesartan group,with irbesartan + Tanzania QiMa low dose group decreased SBP levels was statistically significant compared with SHR group(P<0.05).After 14 weeks,16 weeks compared with SHR group,irbesartan group,irbesartan + QiMa low dose group,high dose group QiMa SBP level decreased significantly,the difference was statistically significant(P<0.05);QiMa SBP low dose group decreased,compared with the SHR group showed no significant difference.3.Compared with before treatment,irbesartan group,SBP decreased at second weeks,the difference was statistically significant(P<0.05),fourth weeks,6 weeks,SBP had no significant change(P>0.05),after eighth weeks,SBP was decreased,the difference was statistically significant(P<0.01);irbesartan + QiMa low dose group from the beginning of the eighth week,SBP decreased significantly(P<0.01);QiMa high dose group,from the beginning of the tenth week SBP decreased(P<0.05 or P<0.01);QiMa low dose group showed no significant change(P>0.05).(?)The effect of compound QiMa Capsule on serum NO,ET-1,Ang?,ACE in SHR1.Serum NO:Compared with the WKY group,SHR group,serum NO level is lower than the WKY group,the difference was statistically significant(P<0.01);compared with SHR group,Irbesartan Capsules group,Irbesartan Capsules+ QiMa,QiMa high dose group all increased serum NO level,the difference was statistically significant(P<0.01 or P<0.05).2.Serum ET-1:Compared with WKY group,ET-1 group,the level of serum SHR increased significantly,the difference was statistically significant(P<0.01);compared with the SHR group,Irbesartan Capsules + QiMa group serum ET-1 levels were significantly decreased,the difference was statistically significant(P<0.01);QiMa low dose group serum ET-1 levels also decreased significantly,there was statistical significant differences(P<0.05).3.Serum ACE:Compared with WKY group,SHR group increased the serum level of ACE,the difference was statistically significant(P<0.05);compared with SHR group,irbesartan group serum ACE levels were significantly reduced,the difference was statistically significant(P<0.05).4.Serum Ang?:Compared with WKY group,SHR group of serum Ang levels were significantly increased,the difference was statistically significant(P<0.01);compared with SHR group,Irbesartan Capsules group,Irbesartan + QiMa group,QiMa low dose group,high dose group QiMa Ang II levels were significantly decreased,the difference was statistically significant(P<0.05).(?)The effect of compound QiMa Capsule on vascular remodeling in SHRs1.Comparison of carotid artery morphology:each rat carotid artery after HE staining under the light microscope,in WKY group,carotid artery intimal smooth,endothelial cell integrity,no shedding,smooth muscle cells arranged in neat,no cell hyperplasia;carotid intima of group SHR is not smooth,the endothelial cells can be seen shedding of smooth muscle cell hypertrophy and hyperplasia,irregular arrangement;irbesartan group,irbesartan+QiMa group showed carotid artery endothelial smooth,no endothelial cell loss,cell arrangement rules,no smooth muscle cell proliferation;QiMa low dose group,high dose group QiMa carotid artery endothelial cells occasionally fall off,smooth muscle cells arranged in neat elastic;fibers arranged in an orderly manner.2.The expression of collagen I carotid artery:WKY group of type I collagen is mainly expressed in smooth muscle cytoplasm,the expression in the normal state;compared with WKY group,SHR group of type I collagen expression increased significantly(P<0.05);compared with SHR group,irbesartan group,irbesartan + QiMa capsule group,low type I collagen expression in lower dose group(P<0.05).3.The expression of carotid artery in type III collagen:compared with WKY group,SHR group of type III collagen expression increased significantly(P<0.05);compared with SHR group,irbesartan group,irbesartan + QiMa group type III collagen expression decreased(P<0.05),the difference was statistically significant?(?)Effects of ACE2-Ang(1-7)-Mas-ERK signaling pathway1.Serum ACE2:Compared with the WKY group,SHR group,serum ACE2 levels decreased,the difference was statistically significant(P<0.01);compared with SHR group,Irbesartan Capsules + QiMa group,QiMa high dose group serum ACE2 levels were significantly increased,the difference was statistically significant(P<0.05).2.Serum Ang(1-7):Compared with WKY group,SHR group of serum Ang(1-7)levels decreased,the difference was statistically significant(P<0.01);compared with SHR group,Irbesartan Capsules group,Irbesartan Capsules +QiMa group and QiMa high dose group serum Ang(1-7)level increased significantly,the difference was statistically significant(P<0.05).3.Expression of ACE mRNA:Compared with WKY group,ACE mRNA expression of SHR group increased significantly(P<0.01);compared with SHR group,the expression level of Irbesartan Capsules group ACE mRNA decreased significantly(P<0.05).4.The expression level of mRNA ACE2:Compared with WKY group,ACE2 mRNA group reduced the expression of SHR(P<0.05);compared with group SHR,Irbesartan Capsules + QiMa group ACE2 increased expression of mRNA(P<0.05);compared to Irbesartan Capsules + QiMa group and QiMa high dose group,the difference was statistically significant(P<0.05).5.The expression level of mRNA Mas:Compared with the WKY group,the expression of SHR Mas mRNA group decreased significantly(P=<0.01);compared with SHR group,Irbesartan Capsules group,irbesartan + QiMa group and QiMa high dose group increased expression mRNA of Mas(P<0.05).6.The expression of pERKl/2 protein:Compared with the WKY group,SHR group,pERKl/2 protein expression level increased(P<0.05);compared with SHR group,Irbesartan Capsules group,Irbesartan Capsules + QiMa group and QiMa high dose group decreased the expression level of pERKl/2 protein significantly(P<0.05).7.The myocardial pathological changes in rats:the rats myocardial tissue after HE staining,placed under the light microscope,the myocardial cells of WKY group arranged neatly,nuclear size uniform,uniform cytoplasmic staining;SHR group myocardial disorder,fracture,part of myocardial hypertrophy,cytoplasmic staining deepened;Irbesartan Capsules group,Irbesartan Capsules + QiMa group showed no obvious myocardial cell hypertrophy,cells arranged in neat;QiMa low dose group,high dose group QiMa myocardial cells are arranged in order,reduce myocardial cell hypertrophy.Cloclusion1.The high dose of compound QiMa capsule can reduce the systolic blood pressure in spontaneously hypertensive rats.2.The compound QiMa capsule can increase the serum NO level of SHR and decrease the level of ET-land Ang?.3.The high dose group of compound QiMa capsule and the combination of compound Shenqi capsule and Western medicine group can reduce the collagen? and ? synthesis and inhibit the vascular remodeling caused by hypertension.4.High dose of compound QiMa capsule can increase the level of ACE2,Ang(1-7)in serum of SHRs.5.Compound QiMa capsule combined with western medicine can increase the expression of ACE2 mRNA in myocardial tissues of rats with SHR alone;Compound QiMa capsule can increase the expression of Mas mRNA SHR in myocardial tissue;Compound QiMa capsule low,high dose of no advantage on the expression of ACE mRNA.6.High dose of compound Shenqi capsule can reduce the expression of pERKl/2 protein in myocardial tissue of SHRs. |
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