右美托咪定通过抑制炎症和自噬减轻毒血症休克大鼠的肺损伤。
Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy.
机构信息
Department of Anesthesiology, Linyi Central Hospital, Linyi, Shandong, China.
Department of Pharmacy, Linyi Central Hospital, Linyi, Shandong, China.
出版信息
Arch Med Res. 2021 Apr;52(3):277-283. doi: 10.1016/j.arcmed.2020.11.001. Epub 2020 Nov 25.
OBJECTIVE
To explore the mechanisms whereby dexmedetomidine reversed lung injury in rats with toxic shock via inhibiting inflammation and autophagy.
METHODS
Thirty-six specific pathogen-free male Sprague Dawley rats with were screened and randomly divided into three groups. Toxic shock was induced by intestinal leakage. The control group received no cecal ligation and the treatment group received dexmedetomidine hydrochloride. Lung tissue morphology was studied by hematoxylin-eosin staining. The expression levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The expression levels of beclin l and LC3 were measured, and the expression levels of apoptosis gene Bax and Bcl-2 were determined. The autophagosomes in lung cells were observed by transmission electron microscopy. Extracellular signal-regulated kinase (ERK) 1/2 expression was determined by Western blotting assays.
RESULTS
The results showed that the W/D, total protein and myeloperoxidase (MPO) index in the toxic shock group were 5.45 ± 0.35, 3.21 ± 0.47 and 4.53 ± 0.36, respectively. The W/D (4.02 ± 0.67), total protein (2.01 ± 0.35) and MPO index (2.31 ± 0.59) were significantly lower in the dexmedetomidine group (p <0.05). Similarly, compared with the toxic shock group, the expression of p-ERK1/2 protein in the dexmedetomidine treatment group was significantly decreased (p <0.05). The expression levels of autophagy proteins beclin1 and LC3 in the dexmedetomidine treatment group were not significantly different from those of the control group (p >0.05). Transmission electron microscopy showed that the number of autophagic bodies in lung cells decreased. After induction with dexmedetomidine hydrochloride, the proapoptotic gene Bax was significantly downregulated in the cells. Bax expression levels in each group were 0.36 ± 0.12, 0.67 ± 0.06, and 0.32 ± 0.12, respectively. Compared with the control group, Bax expression in lung tissue significantly increased in the toxic shock group (p <0.05).
CONCLUSION
Dexmedetomidine attenuates lung injury in toxic shock rats by inhibiting inflammation and autophagy.
目的
通过抑制炎症和自噬，探讨右美托咪定逆转毒血症大鼠肺损伤的机制。
方法
筛选并随机将 36 只无特定病原体的雄性 Sprague Dawley 大鼠分为三组。肠漏诱导毒血症。对照组不行盲肠结扎，治疗组给予盐酸右美托咪定。通过苏木精-伊红染色研究肺组织形态。采用逆转录-聚合酶链反应（RT-PCR）测定肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）等炎症细胞因子的表达水平。测定自噬基因 beclin1 和 LC3 的表达水平，测定凋亡基因 Bax 和 Bcl-2 的表达水平。通过透射电镜观察肺细胞中的自噬体。采用 Western blot 法测定细胞外信号调节激酶（ERK）1/2 的表达。
结果
结果显示，毒血症组的 W/D、总蛋白和髓过氧化物酶（MPO）指数分别为 5.45±0.35、3.21±0.47 和 4.53±0.36。与毒血症组相比，右美托咪定组的 W/D（4.02±0.67）、总蛋白（2.01±0.35）和 MPO 指数（2.31±0.59）明显降低（p<0.05）。同样，与毒血症组相比，右美托咪定治疗组的 p-ERK1/2 蛋白表达明显降低（p<0.05）。右美托咪定治疗组自噬蛋白 beclin1 和 LC3 的表达水平与对照组无明显差异（p>0.05）。透射电镜显示，肺细胞内自噬体数量减少。用盐酸右美托咪定诱导后，细胞中促凋亡基因 Bax 明显下调。各组 Bax 表达水平分别为 0.36±0.12、0.67±0.06 和 0.32±0.12。与对照组相比，毒血症组肺组织 Bax 表达明显升高（p<0.05）。
结论
右美托咪定通过抑制炎症和自噬减轻毒血症大鼠的肺损伤。
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