Atorvastatin Attenuates Cold-induced Hypertension by Preventing Gut Barrier Injury.
Atorvastatin Attenuates Cold-induced Hypertension by Preventing Gut Barrier Injury.
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DOI：
10.1097/fjc.0000000000000690
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发表时间：
2019-08
影响因子：
3
通讯作者：
Song Zhang;Yun Zhang;Mian Zeeshan Ahsan;Yue Yuan;Guang-zhong Liu;Xuejie Han;Jia-wei Zhang;Xinbo Zhao;Bing Bai;Yue Li
中科院分区：
文献类型：
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作者：
Song Zhang;Yun Zhang;Mian Zeeshan Ahsan;Yue Yuan;Guang-zhong Liu;Xuejie Han;Jia-wei Zhang;Xinbo Zhao;Bing Bai;Yue Li
长期暴露在寒冷中会导致动脉高血压(CIH)。越来越多的数据表明，肠屏障功能障碍参与了高血压的发病机制。在本研究中，我们探讨了肠屏障功能障碍对冷暴露诱导的血管炎症的影响以及阿托伐他汀对脑出血大鼠的治疗作用。冷暴露2周建立脑出血模型。两组SD大鼠均暴露于中等温度(4±1℃)，对照组维持在室温(23±1℃)(10只/组)。两组分别在冷暴露开始时接受阿托伐他汀或赋形剂治疗，为期两周。与RT组相比，冷暴露使平均动脉压(MAP)升高，表明动物发生了动脉高血压。冷暴露导致血管功能障碍，这是由于主动脉中磷酸化eNOS蛋白表达减少所致，阿托伐他汀可使其减弱。冷暴露可增加肠源性炎性细胞因子、肿瘤坏死因子-α和白介素6的水平，并导致血管炎症，而阿托伐他汀可阻止这些作用。冷暴露还增加肠道通透性，抑制近端结肠紧密连接蛋白的表达，并导致肠屏障功能障碍。有趣的是，阿托伐他汀消除了肠通透性增加、紧密连接蛋白表达减少、肠道病理和逆转肠屏障功能障碍。阿托伐他汀可减轻脑出血，改善肠屏障功能，其机制可能与抑制肠源性炎症细胞因子和逆转冷诱导的血管炎症有关，提示肠屏障功能障碍可能参与脑出血的发病机制。
Chronic exposure to cold causes arterial hypertension (CIH). Emerging data have indicted that gut barrier dysfunction is involved in the pathogenesis of hypertension. In this study we explored the effect of gut barrier dysfunction on vascular inflammation induced by cold exposure and the therapeutic effect of atorvastatin in a CIH rat model. The CIH was established by cold exposure for two weeks. Two groups of Sprague Dawley (SD) rats were exposed to moderate cold (4 ± 1 °C), while the control group was maintained at room temperature (RT) (23 ± 1 °C) (10 rats/group). The two groups were received atorvastatin or vehicle at beginning of cold exposure, respectively, for two weeks. Cold exposure increased mean arterial pressure (MAP) compared to RT group, indicating that animals developed arterial hypertension. Cold exposure induced vascular dysfunction due to decreasing phosphorylated eNOS protein expression in aorta, and these were blunted by atorvastatin. Cold exposure increased the levels of gut-derived inflammatory cytokines, TNF-α and IL-6 production in aorta, and resulted in vascular inflammation, while atorvastatin prevented these effects. Cold exposure also increased gut permeability, inhibited tight junction protein expression in proximal colon and resulted in gut barrier dysfunction. Interestingly, atorvastatin eliminated increasing of gut permeability, decreasing of tight junction protein expression, gut pathology and reversed gut barrier dysfunction. Atorvastatin attenuated CIH and improved gut barrier function, the beneficial effects might be via inhibiting gut-derived inflammatory cytokines and reversing cold-induced vascular inflammation, suggesting that gut barrier dysfunction may be involved in the pathogenesis of CIH.