瑞舒伐他汀可减轻大鼠肠道缺血再灌注损伤，这与内皮型一氧化氮合酶蛋白的保留有关。
Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with the preservation of endothelial nitric oxide synthase protein.
作者信息
Naito Yuji, Katada Kazuhiro, Takagi Tomohisa, Tsuboi Hisato, Kuroda Masaaki, Handa Osamu, Kokura Satoshi, Yoshida Norimasa, Ichikawa Hiroshi, Yoshikawa Toshikazu
机构信息
Department of Medical Proteomics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
出版信息
World J Gastroenterol. 2006 Apr 7;12(13):2024-30. doi: 10.3748/wjg.v12.i13.2024.
AIM
To investigate the protective effect of rosuvastatin on ischemia-reperfusion (I-R)-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase (eNOS) protein.
METHODS
Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot.
RESULTS
The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissue-associated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattractant-1 (CINC-1) and tumor necrosis factor-alpha (TNF-alpha). These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvastatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-alpha was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin.
CONCLUSION
Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.
目的
研究瑞舒伐他汀对大鼠缺血再灌注（I-R）诱导的小肠损伤和炎症的保护作用，并确定该药物对内皮型一氧化氮合酶（eNOS）蛋白表达的影响。
方法
通过夹闭雄性Sprague-Dawley大鼠的肠系膜上动脉和腹腔干30分钟，随后再灌注60分钟来诱导肠道损伤。在缺血前60分钟腹腔注射溶解于生理盐水中的瑞舒伐他汀。通过多种生化标志物以及组织学检查结果评估肠黏膜损伤和炎症的严重程度。通过蛋白质印迹法测定eNOS的蛋白水平。
结果
与假手术组相比，I-R组中作为黏膜损伤指标的腔内血红蛋白和蛋白水平均显著升高。然而，瑞舒伐他汀治疗以剂量依赖性方式显著抑制了这些升高。瑞舒伐他汀的保护作用也通过组织学检查结果得到证实。小肠暴露于I-R导致黏膜炎症，其特征为硫代巴比妥酸反应性物质、组织相关髓过氧化物酶活性以及大鼠细胞因子诱导的中性粒细胞趋化因子-1（CINC-1）和肿瘤坏死因子-α（TNF-α）的黏膜含量显著增加。I-R后这些炎症参数的增加被10mg/kg剂量的瑞舒伐他汀预处理显著抑制。此外，I-R后CINC-1和TNF-α的mRNA表达增加，且这种增加也被瑞舒伐他汀抑制。I-R期间eNOS的黏膜蛋白水平下降，但在接受瑞舒伐他汀治疗的大鼠中得以保留。
结论
瑞舒伐他汀抑制I-R诱导的大鼠肠道损伤和炎症，其保护作用与eNOS蛋白的保留有关。
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