Comparison of Sex and Dose Differences in Doxorubicin-Induced Myocardial Fibrosis in Rats
YANG Xiaowei1, ZHANG Sihan2, PAN Liangliang1, WANG Xueqing1, WANG Shaolan1, LI Mi1, MA Xiaozhen1, YU Yuanwang1*
This study investigated gender-related and dose-related differences in the sensitivity of SD (Sprague-Dawley) rats to doxorubicin-induced cardiac fibrosis. Fifty-six 6- to 8-week-old SD rats (equal numbers of males and females) were divided into 8 groups based on sex and cumulative DOX doses [0 (saline control), 12, 15, or 18 mg/kg] to establish a myocardial fibrosis model via intraperitoneal injection. In this study, the present experiment established an animal model of myocardial fibrosis induced by intraperitoneal injection. To comprehen sively evaluate the model, assessments were conducted at multiple levels: cardiac function was assessed by ECG (electrocardiography) and echocardiography; relevant pathophysiological changes were reflected by measuring serum levels of BNP (B-type natriuretic peptide) and E2 (estradiol); and the extent of myocardial fibrosis was directly determined by cardiac histopathological analysis. Results display under equivalent DOX doses, male rats exhibited significantly greater reductions in heart rate (P<0.001), prolonged QT intervals (P<0.05), decreased left ventricular ejection and fractional shortening (P<0.05), elevated serum BNP (P<0.01), increased myocardial collagen deposi tion (P<0.01), and more pronounced reductions in serum E2 (P<0.01) compared to females. Dose-dependent analy sis revealed progressive cardiac dysfunction and aggravated myocardial fibrosis across all groups with increasing DOX doses. Male rats showed significant myocardial damage at 15 mg/kg, whereas females required 18 mg/kg to manifest comparable injury. Histopathology confirmed more severe inflammatory infiltration and fibrotic lesions in males at identical doses. The conclusion shows DOX-induced myocardial fibrosis in SD rats demonstrates both dose dependence and sex dimorphism, with males exhibiting higher susceptibility than females. The relative resis tance in females may be attributed to estrogen-mediated cardioprotective mechanisms.
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