| Objective:To explore the composing principles of the herbal paste,and summarize the clinical experience of professor Chen in essential hypertension by using the Traditional Chinese Medicine Inheritance Support System(TCMISS).Then observe the effects of different doses of herbal paste on ventricular remodeling and myocardial autophagy,to investigate the possible mechanism of them in spontaneously hypertension rats(SHR).Methods:Collecting the prescriptions of patients who have hypertension and treated by doctor Chen during October 23,2018 to December 28,2018,then input them into the TCMISS,make statistics of herbals which used frequently and make associative analysis and cluster analysis of them,so finally we can find the medication rules of doctor Chen's herbal paste.Fifty 12-month-old male SHR were randomly divided into five groups:low-dosage paste group(L),medium-dosage paste group(M),high-dosage paste group(H),general-dosage irbesartan group(I)and blank group(C),ten 12-month-old healthy male Wistar-Kyoto rats as the control group(W).After adaptive feeding,all rats were given different dosage of herbal paste or irbesartan and isodose distilled water.At the end of experiment,the heart weight index(HWI)were measured,the pathological changes of ventricular muscle sections were observed by HE staining,Beclin1 protein,phosphorylated mTOR protein,phosphorylated Akt protein,PTEN protein expressions were analyzed by Western blot.Results:1.In data mining:After analyzing 106 prescriptions,several high-frequency herbs were fond which includes gastrodiae,fructus corni,radix rehmanniae,rhizoma alismatis,rhizoma atractylodis,etc.Among these herbs,the nature is mostly warm and the flavor is mostly sweet,liver,kidney and spleen meridians are predominated.Through association analysis,several highly relevant herbal pairs were discovered,such as fructus corni-gastrodiae,radix rehmanniae-gastrodiae,radix rehmanniae-fructus corni,rhizoma alismatis-gastrodiae,rhizoma atractylodis-gastrodiae,etc.Through cluster analysis,we obtain 28 core combination modes and 14 neo prescriptions.2.In animal experiments:After four weeks of oral administration,compared to C group,H group and I group obviously reduced in HWI and the myocardial cell hypertrophy was alleviated,the myocardial cells were neatly arranged,the fibrogenesis was also reduced.Compared to W group,the expression levels of Beclin1 protein of C group were significantly increased(P<0.05),and the expression levels of Beclin1 protein of M group were significantly decreased than C group(P<0.05).The expression levels of PTEN protein of L group,M group and H group had different degrees of reduction(P<0.05).The expression levels of mTOR protein and phosphorylated mTOR protein of all paste group were increased,but it can't make statistical significance(P>0.05).Compared to C group,the expression levels of Akt protein and phosphorylated Akt protein of H group had a significant increase(P<0.05).Conclusion:The analysis shows that the view of doctor Chen on hypertension i.s to supplement liver and kidney,tranquilize liver and yang;take care of digestive system,prevention before illness;benefit body by using warm and sweet herbs,reinforcing yang qi by nourishing yin,which is in line with the popular treatments of hypertension.Herbal paste intervention can reduce the HWI of SHR,lighten myocardial hypertrophy and ameliorate myocardial remodeling;The expression levels of autophagy related protein in SHR were increased,but herbal paste can make it decline to varying degrees and improve the expression of signaling protein in PI3K/Akt/mTOR signal path,which indicates that autophagy is enhanced in SHR when ventricular remodeling happened,herbal paste can inhibit the autophagy of SHR and its mechanism maybe achieved by inhibiting PTEN protein and stimulating phosphorylated mTOR protein and phosphorylated Akt protein.The results seem to prompt the adverse effects of autophagy on some stage during the process of myocardial hypertrophy and remodeling. |
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