评价激活α7烟碱型乙酰胆碱受体对大鼠呼吸机相关肺损伤的影响。

采用随机数字法将32只雄性Sprague Dawley大鼠分为：对照组（C组）、机械通气组（V组）、烟碱预处理+机械通气组（N组）、甲基牛扁碱（MLA）+烟碱+机械通气组（MLA组），每组8只。C组大鼠气管插管后不进行机械通气，保留自主呼吸，其余各组大鼠机械通气2 h。N组大鼠在机械通气前30 min腹腔注射1 mg/kg的烟碱；MLA组大鼠在腹腔注射烟碱前30 min先腹腔注射1 mg/kg的MLA，其余各组大鼠腹腔注射等量等渗NaCl溶液。机械通气结束后即刻处死大鼠，计算各组大鼠肺组织湿重/干重、苏木素-伊红（HE）染色、肺组织损伤病理学评分，并采用Western-blotting检测白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）蛋白表达水平。

C组大鼠肺泡形态结构正常；V组大鼠肺泡形态结构破坏，大量炎症细胞浸润；N组大鼠肺泡形态结构稍破坏，少量炎症细胞浸润；MLA组大鼠肺泡形态结构破坏，肺泡萎陷，较多炎症细胞浸润。4组大鼠肺组织湿重/干重、损伤评分、IL-1β、IL-6及TNF-α蛋白表达水平比较，差异均有统计学意义（F = 168.009、647.579、138.005、192.706、178.094，P均< 0.05）。进一步两两比较发现，V组大鼠肺组织湿重/干重、损伤评分、IL-1β、IL-6、TNF-α蛋白表达水平均较C组更高（P均< 0.05）；N组大鼠湿重/干重、损伤评分、IL-1β、IL-6、TNF-α蛋白表达水平均较V组明显降低（P均< 0.05）；MLA组大鼠肺组织湿重/干重、损伤评分、IL-1β、IL-6、TNF-α蛋白表达水平均较N组明显升高，差异有统计学意义（P均< 0.05）。

烟碱对呼吸机相关肺损伤的大鼠模型具有保护作用，其机制与激活α7-nAChR有关。

To evaluate the activation effect of α7 nicotinic acetylcholine receptor (α7-nAChR) on ventilator-induced lung injury in rats.

Thirty-two male Sprague Dawley rats were randomly divided into four groups: the control group (C group), mechanical ventilation group (V group), nicotine pretreatment and mechanical ventilation group (N group), and methylbovine (MLA), nicotine and ventilation group (MLA group), with 8 rats in each group. Rats in the C group did not undergo mechanical ventilation after tracheal intubation, while the rest were mechanically ventilated for 2 hours. Rats in the N group were intraperitoneally injected with 1 mg/kg nicotine 30 min before mechanical ventilation, rats in MLA group were injected with 1 mg/kg MLA 30 min before intraperitoneal injection of niacin, and rats in other groups were intraperitoneally injected with isotonic sodium chlorrde solution. Rats were sacrificed immediately after mechanical ventilation. The wet/dry weight of lung tissue, hematoxylin eosin (HE) staining and pathological score of lung injury were calculated. The expression levels of interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) protein were detected by Western-blotting.

The alveolar morphology of rats was normal in the C group; alveolar morphology was destroyed, and a large number of inflammatory cells infiltrated in V group. The alveolar morphology was slightly destroyed, and a small number of inflammatory cells infiltrated in N group. The alveolar structure was destroyed, alveolus collapsed, and more inflammatory cells infiltrated in MLA group. There were significant differences in the wet/dry weight, injury score, and expressions of IL-1β, IL-6 and TNF-α protein of lung tissue among these four groups (F = 168.009, 647.579, 138.005, 192.706, 178.094; all P < 0.05). Further comparison showed that the wet/dry weight, injury score, and expressions of IL-1β, IL-6 and TNF-α protein of lung tissue were significantly higher in the V group than in C group (all P < 0.05), significantly lower in N group than in V group (all P < 0.05), and significantly higher in MLA group than in N group (all P < 0.05).

Nicotine has a protective effect on ventilator-induced lung injury in rats, and its mechanism is related to the activation of α7-nAChR.