| AIM:To observe the antihypertensive effect of rhynchophylline on renal hypertension rats and the improvement of myocardial hypertrophy and to discuss the possible mechanism.Methods:Male SD rats were used in the experiment,and the operation method of"two kidneys and one clip"was adopted to establish the model of renal hypertension rats,which were divided into the experimental group,the sham operation group,the positive control group and the model control group.The drugs in the experimental group were given high doses of rhynchophylline(10 mg·kg-1·d,n=8)and low doses of rhynchophylline(2.5 mg·kg-1·d,n=8).The positive control group was given captopril（12.5 mg·kg-1·d,n=8）.The model group was given the same amount of normal saline for8 weeks,and the blood pressure of the rats was measured every 2 weeks.The body mass（BW）of rats in each group was measured before the rats were sacrificed,and the bilateral renal morphology of rats in each group was compared and observed after the rats were sacrificed.After cardiac treatment,the whole heart wet weight（HWW）was measured,and the whole heart mass index（HMI=HWW/BW）was calculated;ELISA kit for determination of angiotensinⅡin blood（AngⅡ）,determination of malondialdehyde in the myocardial tissue（MDA）,oxide dismutase（SOD）,glutathione reductase（GR）,glutathione S transferase（GST）and glutathione peroxidase（Gsh-px）content.The content of free fatty acid（FFA）in blood supernatant and myocardium were determined.Western Blot method to measure the myocardial tissue of nuclear factor kappaκB（nf-κB）predominate and transforming growth factorβ1（TGF-β1）,hypoxia inducing factor 1α（HIF-1α）,peroxidase body growth activated receptorα/γ（PPARα/γ）,glycerin-3-phosphate acyltransferase（GPAT）,carnitine palmitic acid transferase1α（CPT 1α）,pyruvate dehydrogenase kinase 4（PDK-4）,glucose transporter 4（GLUT-4）protein expression.Results:（1）two kidney one clip 4 weeks after surgery,systolic blood pressure（SBP）and diastolic blood pressure（DBP）of model group rats increased significantly in the control group（P<0.01）,after eight weeks,SBP,DBP,compared with the model group rats,rhy numerical high and low dose group were different degrees of decline（P<0.05or P<0.01）,and at the start of the 6 weeks to numerical gradually stabilized level;（2）after 8 weeks of administration in each group,the heart and organ indexes of the model group were significantly increased（P<0.01）,and the heart and organ indexes of the high and low dose groups of rhynchophylline treatment showed a certain degree of decrease（P<0.05 or P<0.01）compared with the model group,and the decrease effect of the high dose group was more significant than that of the low dose group（P<0.01）.In serum AngⅡ,rhy can make in the serum AngⅡcontent decreased significantly（P<0.05 or P<0.01）.（3）after 8 weeks of administration,HE staining showed that hypertrophy or even hyperplasia occurred in the rat cardiac myocytes of the model group,with deepened staining of the nuclei and enlarged interstitial space between the cardiac myocytes.The above pathological changes were improved in the high and low dose groups,and the effect was more significant in the high dose group.（4）after 8 weeks of administration,compared with the sham operation group,the level of free fatty acid（FFA）in the blood supernatant of rats in the model group also decreased significantly（P<0.05）.MDA content in myocardium was decreased to some extent,especially in the high-dose group（P<0.05 or P<0.01）.Rhynchophylline can also increase the levels of SOD,GR,GST and gsh-px in serum and cardiac tissue（P<0.05or P<0.01）.（5）Western Blot results showed that rhynchophylline significantly down-regulated the protein expressions of NF-κB,TGF-β1,HIF-1α,PPARα,GPAT and GLUT-4 in hypertrophic myocardium（P<0.05 or P<0.01）.The protein expressions of PPARγ,CPT-1αand PDK-4 in hypertrophic myocardium were significantly up-regulated（P<0.05 or P<0.01）. |
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