Wang Yu, Wang Xiaofeng, Yang Wenping, Zhao Xin, Zhang Rong
Emergency Department, Shengjing Hospital affiliated to China Medical University, Shenyang, Liaoning Province, China.
Emergency Department, Shengjing Hospital affiliated to China Medical University, Shenyang, Liaoning Province, China.
J Surg Res. 2018 Dec;232:531-538. doi: 10.1016/j.jss.2018.07.016. Epub 2018 Aug 3.
Simvastatin may alleviate the intestinal barrier dysfunction induced by sepsis. This study aimed to investigate the role of the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway in the intestinal barrier of simvastatin-treated rats with sepsis.
Male Wistar rats were pretreated with simvastatin (0.2 μg/g of body weight) for 1 week before cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, the condition of bacterial translocation was evaluated. Plasma levels of intestinal fatty acid binding protein, D-lactic acid and inflammatory factors, and oxidative stress in the intestine were determined. The intestinal injury scores, as well as the protein levels of Rho, ROCK1, and tight junction proteins ZO-1 and occludin were analyzed.
Treatment with simvastatin alleviated the sepsis-induced increases in the plasma concentration of intestinal fatty acid binding protein and D-lactic acid, as well as the number of colony-forming units in the bacterial culture of the blood, liver, spleen, and kidney. In addition, simvastatin effectively reduced the intestinal levels of tumor necrosis factor α, interleukin-6, high-mobility group box 1, and malondialdehyde and increased the activity of superoxide dismutase in rats with sepsis. Staining with hematoxylin and eosin showed that severe intestinal injury occurred in the sepsis group, which was reduced by the treatment of simvastatin. Furthermore, the expression of Rho and ROCK1 was significantly downregulated and the protein expression levels of ZO-1 and occludin were significantly increased in simvastatin-treated rats (P < 0.05).
Simvastatin can ameliorate the intestinal barrier dysfunction caused by sepsis by inhibiting the Rho/ROCK signaling pathway and reducing the levels of inflammatory factors and oxidative stress in the intestine, which also increase the expression of tight junction proteins.
辛伐他汀可能减轻脓毒症诱导的肠道屏障功能障碍。本研究旨在探讨Ras同源物（Rho）/Rho相关卷曲螺旋形成蛋白激酶（ROCK）信号通路在辛伐他汀治疗的脓毒症大鼠肠道屏障中的作用。
雄性Wistar大鼠在盲肠结扎和穿刺前1周用辛伐他汀（0.2μg/g体重）预处理。盲肠结扎和穿刺24小时后，评估细菌移位情况。测定血浆中肠脂肪酸结合蛋白、D-乳酸和炎症因子水平以及肠道氧化应激。分析肠道损伤评分以及Rho、ROCK1和紧密连接蛋白ZO-1和闭合蛋白的蛋白水平。
辛伐他汀治疗减轻了脓毒症诱导的血浆中肠脂肪酸结合蛋白和D-乳酸浓度升高，以及血液、肝脏、脾脏和肾脏细菌培养中菌落形成单位的数量。此外，辛伐他汀有效降低了脓毒症大鼠肠道中肿瘤坏死因子α、白细胞介素-6、高迁移率族蛋白B1和丙二醛水平，并增加了超氧化物歧化酶活性。苏木精和伊红染色显示脓毒症组发生严重肠道损伤，辛伐他汀治疗减轻了这种损伤。此外，辛伐他汀治疗的大鼠中Rho和ROCK1的表达显著下调，ZO-1和闭合蛋白的蛋白表达水平显著增加（P<0.05）。
辛伐他汀可通过抑制Rho/ROCK信号通路、降低肠道炎症因子水平和氧化应激，改善脓毒症引起的肠道屏障功能障碍，还可增加紧密连接蛋白的表达。
