Preliminary observation of the effect of vitamin C and adenosine triphosphate on myocardial fibrosis in rats / 中华地方病学杂志

ABSTRACT

Objective To observe the intervention effect of vitamin C (Vit C) and adenosine triphosphate (ATP) on myocardial fibrosis in rats.Methods Forty male SD rats were selected,body weight were 125-140 g,and they were divided into 8 groups according to body weight using a random number table method.Four rats for control group,3 rats for model group,6 rats for Vit C early group,6 rats for ATP early group,6 rats for Vit C + ATP early group,5 rats for Vit C late group,5 rats for ATP late group,and 5 rats for Vit C + ATP late group.Rats in model group and these intervention groups were induced with doxorubicin (2 mg/kg each week) for 6 weeks,and control group was given the same amount of normal saline.All early groups were intragastrically administered with Vit C (200 mg·kg-1·d-1),ATP (45 mg·kg-1·d-1) and Vit C + ATP (200 mg·kg-1·d-1 + 45 mg·kg-1 ·d-1) in the fourth week;these late groups were intragastrically administered with the same dose in the sixth week;each group was continuously administered for 21 days.Three days after the last intervention,cardiac ultrasonography was performed in all surviving rats,and left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD),left ventricular ejection fraction (LVEF),and left ventricular fractional shortening (LVFS) were recorded.The rats were sacrificed and the hearts were taken.HE staining and Masson staining were used to observe the pathological changes of myocardial tissue and the collagen volume fraction (CVF) was calculate.Serum cardiac troponin Ⅰ (CTn-Ⅰ) and type Ⅰ procollagen amino terminal peptide (PINP) levels were determined by enzyme-linked immunosorbent assay (ELISA).Results Compared with control group [(3.65 ± 0.25) mm,(80.63 ± 3.03)％,(43.57 ± 2.54)％],LVESD [(5.07 ± 0.58),(4.06 ± 0.68),(4.71 ± 0.43),(4.87 ± 0.44),(4.79 ± 0.59),(5.07 ± 0.62),(4.97 ± 0.29) mm] of model group and each intervention groups were increased,LVEF [(62.17 ± 4.92)％,(71.28 ± 3.54)％,(65.03 ± 3.35)％,(59.81 ± 2.45)％,(60.42 ± 9.22)％,(60.15 ± 3.06)％,(60.65 ± 2.05)％],and LVFS [(30.05 ± 2.95)％,(36.44 ± 2.90)％,(31.63 ± 2.15)％,(26.95 ± 1.05)％,(28.35 ± 6.84)％,(27.79 ± 2.41)％,(28.38 ± 1.42)％] were decreased (P ＜ 0.05);compared with model group,LVESD was decreased,LVEF and LVFS were increased in Vit C early group (P ＜ 0.05).HE staining showed that the myocardial pathology of each early group improved to different degrees,such as cardiomyocyte degeneration,necrosis and fibrosis,inflammatory cell infiltration,moderate degree of interstitial edema,Vit C early group and Vit C + ATP early group were more pronounced.Masson staining showed significant improvement in fibrosis in the Vit C early group and Vit C + ATP early group,and collagen fibers were significantly reduced.Compared with the control group [(0.52 ± 0.14)％],the CVF [(27.11 ± 5.05)％,(9.80 ± 1.84)％,(16.55 ± 2.21)％,(5.06 ± 1.45)％,(12.11 ± 2.12)％,(15.71 ± 1.56)％,(16.93 ± 2.76)％] of myocardial tissue in model group and each intervention groups were significantly increased (P ＜ 0.05).There were no significant differences in CTn-Ⅰ and PINP levels between the eight groups (P ＞ 0.05).Conclusions Vit C can reduce myocardial fibrosis and improve cardiac function in the early stage.The effect of ATP alone to improve fibrosis is not obvious.