罗汉果皂苷V对胎粪吸入综合征大鼠的保护作用及其初步机制研究

Protective effect and possible mechanism of mogroside V in rats with meconium aspiration syndrome

目的 观察罗汉果皂苷V对胎粪吸入综合征(MAS)大鼠急性肺损伤的保护作用,并初步探讨其作用机制。方法 将48只健康Wistar大鼠随机分为假手术组、模型组、罗汉果皂苷V低、中、高剂量组(2.5、5、10 mg/kg)和地塞米松组(0.5 mg/kg),8只/组;采用经口直视气管插管法构建MAS模型;罗汉果皂苷V低、中、高剂量组及地塞米松组于造模后灌胃给药,模型组和假手术组给予等量生理盐水灌胃。采用HE染色观察肺组织病理变化;测量肺组织湿干质量比(W/D);ELISA法检测血清和肺泡灌洗液肿瘤坏死因子α(TNF-α)、白介素6(IL-10)、白介素1β(IL-1β)水平;比色法检测肺组织中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;Western blot检测肺组织c-Jun氨基末端激酶(JNK)、磷酸化JNK(p-JNK)蛋白表达。结果 与假手术组比较,模型组肺组织病理评分、W/D升高(P<0.05),肺泡灌洗液及血清TNF-α、IL-6、IL-1β水平升高(P<0.05),肺组织MDA与MPO水平升高、SOD水平降低(P<0.05),肺组织p-JNK蛋白表达水平上调(P<0.05)。与模型组比较,罗汉果皂苷V中、高剂量组及地塞米松组肺组织病理评分、W/D降低(P<0.05),肺泡灌洗液及血清TNF-α、IL-6、IL-1β水平降低(P<0.05),肺组织MDA与MPO水平降低、SOD水平升高(P<0.05);罗汉果皂苷V中、高剂量组肺组织p-JNK蛋白表达水平下调(P<0.05)。结论 罗汉果皂苷V可能通过抑制JNK磷酸化,减轻MAS病程中炎性和氧化应激损伤而发挥急性肺损伤保护作用。

Objective To observe the protective effect of mogroside V against acute lung injury in rats with meconium aspiration syndrome(MAS) and to explore its possible mechanism.Methods Forty-eight healthy Wistar rats were randomly divided into sham operation,model,low-,medium-and high-dose mogroside V groups(2.5,5 and 10 mg/kg) and a dexamethasone group(0.5 mg/kg) with eight mice per group.MAS models were established by oral tracheal intubation.After modeling,low-,medium-and high-dose mogroside V groups,and the dexamethasone group were administered the indicated doses of drugs,whereas model and sham operation groups were administered the same volume of normal saline.Pathological changes of lung tissues were observed by HE staining.The wet-to-dry weight ratio(W/D) of lung tissues was calculated.The levels of tumor necrosis factor α(TNF-α),interleukin(IL)-6,and IL-1β in serum and bronchoalveolar lavage fluid were measured by ELISA.Malondialdehyde(MDA) and activity of superoxide dismutase(SOD) in lung tissues were detected by colorimetry.Protein expression of c-Jun N-terminal kinase(JNK) and phosphorylated JNK(p-JNK) in lung tissues was detected by Western blot.Results Compared with the sham operation group,the pathological score of lung tissues and W/D were increased(P<0.05),TNF-α,IL-6 and IL-1β levels were increased in bronchoalveolar lavage fluid and serum(P<0.05),MDA and MPO were increased in lung tissues,the SOD level was decreased(P<0.05),and p-JNK protein expression in lung tissues was upregulated in the model group(P<0.05).Compared with the model group,the pathological score of lung tissues and W/D were decreased(P<0.05),TNF-α,IL-6 and IL-1β levels were decreased in bronchoalveolar lavage fluid and serum(P<0.05),MDA and MPO were decreased in lung tissues,while the SOD level was increased in medium-and high-dose mogroside V groups,and the dexamethasone group(P<0.05).p-JNK protein expression was downregulated in lung tissues in medium-and high-dose mogroside V groups(P<0.05).Conclusions Mogroside V may reduce inflammatory and oxidative stress damage in MAS rats by inhibiting JNK phosphorylation and thus protect them against acute lung injury.