Objective  To analyze the injury of sepsis to myocardial tissue and myocardial mitochondria in rats, and to investigate the effects of alprostadil combined with Xuebijing on myocardial injury and mitochondrial structure in septic rats.

Methods Ninety SPF healthy adult male SD rats were randomly divided into the sham operation group (Sham group), sepsis group (CLP group), alprostadil group (Alp group), Xuebijing group (XBJ group), and alprostadil combined with Xuebijing group (Alp + XBJ group), with 18 rats in each group. Except for the Sham group, in which only laparotomy and cecal mobilization were performed, sepsis models were established in the other four groups by cecal ligation and puncture. At 3 h after model establishment, rats in the treatment groups were given intraperitoneal injections of alprostadil (10 μg/kg), Xuebijing (10 mL/kg), or alprostadil combined with Xuebijing, respectively, while rats in the sepsis group were given an equal volume of normal saline by intraperitoneal injection. Ten rats from each group were selected to observe 7-day survival, and the remaining rats were euthanized 24 h after surgery. Serum levels of creatine kinase-MB (CK-MB) and cardiac troponin Ⅰ (cTn Ⅰ) were measured. Histopathological changes in myocardial tissue and mitochondrial ultrastructural changes were observed by HE staining and transmission electron microscopy, respectively. The mitochondrial cross-sectional area and volume density were further quantitatively analyzed using images obtained under transmission electron microscopy.

Results There was a statistically significant difference in the 7-day survival rate among the groups (log-rank test: χ² = 33.587, P ＜ 0.001). The 7-day survival rate in the CLP group was lower than that in the Alp + XBJ group (P = 0.003). No statistically significant differences in 7-day survival were observed among the XBJ, Alp, and Alp + XBJ groups (P = 0.464, 0.330, and 0.074, respectively). Compared with the Sham group, the sepsis group showed increased serum CK-MB and cTn Ⅰ levels (both P ＜ 0.001), disordered myocardial tissue structure, and inflammatory cell infiltration. Under electron microscopy, mitochondrial swelling, cristae disruption, and vacuolar degeneration were observed, with increases in mitochondrial cross-sectional area and volume density (both P ＜ 0.001). Under the sepsis model, two-way analysis of variance showed that the main effects of alprostadil and Xuebijing in reducing CK-MB and cTn Ⅰ levels were statistically significant (all P ＜ 0.05), and an interaction effect was also observed between the two treatments (F = 10.98, P = 0.003; F = 9.63, P = 0.004), the estimated marginal means plot showed that the combination therapy had a synergistic effect. In terms of ultrastructure, both drugs improved mitochondrial cross-sectional area and volume density (both P ＜ 0.001), and the combination therapy showed superior improvement in mitochondrial cross-sectional area compared to each monotherapy group (both P < 0.05).

Conclusions Sepsis can lead to myocardial injury and mitochondrial structural damage in rats. The combined application of alprostadil and Xuebijing can enhance the cardioprotective effect and shows synergistic effects on some mitochondrial structural indicators.