钙蛋白酶抑制剂Calpeptin 在脓毒症膈肌功能障碍中的作用研究.

This investigation was under taken to explore probable mechanisms and signal pathways involved in diaphragm dysfunction induced by Sepsis. The rat sepsis model was constructed by injecting 8 mg/kg LPS into the abdominal cavity. Male SD rats were divided into 3 groups (n=6/group): comparing control group (Con group), LPS group (Sepsis group) and calcium Protease inhibitor pretreatment group (Calpeptin group). Each group of rats was sacrificed, and then their diaphragm tissues were quickly separated. The pathological changes of the diaphragm tissue were observed by using the hematoxylin-eosin (HE) staining method. Additionally, the mRNA expression levels ofμ-Calpain, caspase-3, Beclin-1, TNF-αand IL-6 in diaphragm tissue were detected by real-time fluorescence quantitative PCR (qRT-PCR). Under the light microscope, we could see that the diaphragm cross-section in the Con group was regular, with full and orderly muscle fibers, closely spaced muscle fibers, and nuclei distributed along the edge of the lens. In the diaphragm muscle cells of the Con group, there were intact capillary endothelium and no interstitial hyperplasia. Compared with the Con group, HE staining of the sepsis group rats with LPS for 24 h showed no obvious changes in diaphragm atrophy, but the contractiity of the diaphragm decreased, which was consistent with our previous research results. The mRNA expression levels of the above genes in sepsis group were significantly increased (P<0.05), and were significantly decreased after Calpeptin pretreatment(P<0.05) by qRT-PCR. Diaphragm muscles are prone to dysfunction during sepsis. Calpeptin, a calpain inhibitor, can significantly reduce the activation of inflammation, apoptosis and autophagy pathways induced by LPS. [ABSTRACT FROM AUTHOR]