Inhibitor of growth protein-2 silencing alleviates angiotensin Ⅱ-induced cardiac remodeling in mice by reducing p53 acetylation / 南方医科大学学报

OBJECTIVE@#To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism.@*METHODS@#An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg-1 · min-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits.@*RESULTS@#The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression.@*CONCLUSION@#Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.

Effects of Fosinopril on Oxidative Stress and Vascular Function in Experimental Rats With Spontaneous Hypertension / 中国循环杂志

Objective: To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods: The rats were divided into 3 groups: Control group, with normal healthy rats (n=15), Spontaneous hypertension (SH) group (n=15), SH rats received intragastric administration of normal saline and Treatment group (n=15), SH rats received intragastric administration of fosinopril 10mg/(kg?d). All animals were treated for 7 weeks. Caudal artery systolic blood pressure (SBP) was measured at each week. blood levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malonaldehyde (MDA) and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine (Ach)/sodium nitroprusside (SNP) induction. Results: From the 1st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P<0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP<0.05; compared with SH group, Treatment group showed elevated SOD activity (P=0.010), while reduced protein levels of MDA (P=0.021) and ROS (P=0.009). Compared with Control group, SH group had the lower content of NO2-/NO3-(P<0.001); both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P<0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP<0.001. Conclusion: Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.

Clinical Observation of Chronic Congestive Heart Failure Treated with Buzhong Yiqi Wuling Decoction Com-bined with Western Medicine / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of Buzhong yiqi wuling decoction combined with western medicine in the treatment of chronic congestive heart failure(CHF). METHODS:120 CHF patients were divided into observation group and control group by random number table method,with 60 cases in each group. Control group received conventional western medicine treatment as rest,low salt diet and diuretics. Observation group was additionally given Buzhong yiqi wuling decoction,one dose a day,at twice,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Average TCM symptom score, level of plasma NT-proBNP,6 min walk test(6MWT)distance before and after treatment,clinical efficacy and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in average TCM symptom score,level of plasma NT-proBNP and 6MWT distance between 2 groups(P>0.05). After treatment,average TCM symptom score and level of plasma NT-proBNP of 2 groups were decreased significantly,and the observation group was more significant than the control group,with statistical significance(P<0.05);6MWT distance of 2 groups were improved significantly compared to before treatment,and the observation group was significantly longer than the control group,with statistical significance(P<0.05). After treatment,total effective rate of observation group(93.33%)was significantly higher than that of control group(83.33%),with sta-tistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Buzhong yiqi wuling decoction is an ef-fective prescription to treat CHF,and can relieve clinical symptoms,improve the cardiac function,decrease NT-proBNP level and en-hance the patient exercise tolerance with good safety.