首页|连翘苷调节SphK1/S1P/S1PR1信号通路对流感病毒肺炎大鼠肺损伤的影响

连翘苷调节SphK1/S1P/S1PR1信号通路对流感病毒肺炎大鼠肺损伤的影响

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目的 探究连翘苷(KD-1)对流感病毒肺炎大鼠肺损伤的影响以及对鞘氨醇激酶1(SphK1)/1-磷酸鞘氨醇(S1P)/鞘氨醇1磷酸酯受体1(S1PR1)信号通路的调节机制.方法 将Wistar雄性大鼠分为对照组(灌胃等量0.9%NaCl)、模型组(灌胃等量0.9%NaCl)、阳性药物组(灌胃0.02 g·kg-1利巴韦林)、PF-543 组(灌胃 10 mg·kg-1SphK1 抑制药 PF-543 Citrate)和低、高剂量实验组(分别灌胃6.5、13 mg·kg-1KD-1).除对照组外,其余各组大鼠用流感病毒滴鼻建立流感病毒感染肺炎模型.测量大鼠的肺指数,用苏木精-伊红(HE)染色法观察大鼠肺组织的病理损伤情况,用酶联免疫吸附试验(ELISA)法检测支气管肺泡灌洗液(BALF)中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和IL-6的含量,用蛋白质印迹法检测大鼠肺组织中SphK1、S1P、S1PR1蛋白的表达水平.结果 低、高剂量实验组和PF-543组、阳性药物组、模型组、对照组的肺指数分别为(7.62±0.51)、(5.34±0.46)、(6.53±0.52)、(5.48±0.43)、(12.46±0.87)和(4.41±0.32)mg·g-1,IL-1β 含量分别为(47.26±2.05)、(25.18±1.58)、(35.75±1.50)、(27.31±1.67)、(62.37±2.51)和(13.28±1.04)ng·L-1,TNF-α 含量分别为(76.58±4.73)、(51.82±3.90)、(64.81±4.15)、(53.06±3.86)、(98.47±4.92)和(42.71±3.52)ng·L-1,IL-6 含量分别为(57.62±4.29)、(39.06±3.86)、(48.75±3.83)、(41.23±3.61)、(76.92±5.24)和(28.56±3.17)ng·L-1,SphK1 蛋白相对表达水平分别为 1.07±0.08、0.51±0.04、0.65±0.05、0.53±0.04、1.28±0.09和0.36±0.03,S1P蛋白相对表达水平分别 为1.21±0.10、0.57±0.05、0.73±0.06、0.58±0.05、1.39±0.11 和 0.39±0.03,S1PR1 蛋白相对表达水平分别为 0.45±0.03、0.83±0.07、0.64±0.05、0.81±0.07、0.28±0.02和1.03±0.07.模型组的上述指标与对照组比较,低、高剂量实验组、PF-543组、阳性药物组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05).结论 KD-1可能通过抑制SphK1/S1P/S1PR1信号通路减轻流感病毒肺炎大鼠的肺损伤.
Effects of phillyrin on lung injury in rats with influenza virus pneumonia by regulating the SphK1/S1P/S1PR1 signal pathway
Objective To explore the effect of phillyrin(KD-1)on lung injury in rats with influenza virus pneumonia and its regulatory mechanism on the sphingosine kinases 1(SphK1)/sphingosine 1-phosphate(S1P)/S1P receptors 1(S1PR1)signal pathway.Methods Wistar male rats were divided into control group(gavage with equal amount of 0.9%NaCl),model group(gavage with equal amount of 0.9%NaCl),positive drug group(gavage with 0.02 g·kg-1 ribaverin),PF-543 group(gavage with 10 mg·kg-1 SphK1 inhibitor PF-543 Citrate)and experimental-L,-H groups(gavage with 6.5,13 mg·kg-1 KD-1,respectively).Except the control group,the other rats were treated with influenza virus nasal drip to establish influenza virus infection pneumonia model.The lung index of rats was measured;Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of lung tissue in rats;the contents of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and IL-6 in bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA);Western blot was applied to detect the expression levels of SphK1,S1P and S1PR1 proteins in rat lung tissue.Results The lung indices of experimental-L,-H groups,PF-543 group,positive drug group,model group and control group were(7.62±0.51),(5.34±0.46),(6.53±0.52),(5.48±0.43),(12.46±0.87)and(4.41±0.32)mg·g-1;IL-1β content were(47.26±2.05),(25.18±1.58),(35.75±1.50),(27.31±1.67),(62.37±2.51)and(13.28±1.04)ng·L-1;the contents of TNF-α were(76.58±4.73),(51.82±3.90),(64.81±4.15),(53.06±3.86),(98.47±4.92)and(42.71±3.52)ng·L-1;IL-6 content were(57.62±4.29),(39.06±3.86),(48.75±3.83),(41.23±3.61),(76.92±5.24)and(28.56±3.17)ng·L-1;SphK1 protein expression were 1.07±0.08,0.51±0.04,0.65±0.05,0.53±0.04,1.28±0.09 and 0.36±0.03;S1P protein expression were 1.21±0.10,0.57±0.05,0.73±0.06,0.58±0.05,1.39±0.11 and 0.39±0.03;S1PR1 protein expression were 0.45±0.03,0.83±0.07,0.64±0.05,0.81±0.07,0.28±0.02 and 1.03±0.07,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P<0.05);compared with the model group,the above indexes in experimental-L,-H groups,PF-543 group and positive drug group had statistical significance(all P<0.05).Conclusion KD-1 may alleviate lung injury in rats with influenza virus pneumonia by inhibiting the SphK1/S1 P/S1 PR1 signal pathway.

phillyrinsphingosine kinases 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptors 1 signal pathwayinfluenza viruspneumonialung injury

刘海燕、付明月、孙海珍、曾玉英

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青海红十字医院感染科,青海西宁 810000

青海红十字医院消化内科,青海西宁 810000

西宁市妇幼保健计划生育服务中心中医科,青海西宁 810000

连翘苷 鞘氨醇激酶1/1-磷酸鞘氨醇/鞘氨醇1磷酸酯受体1信号通路 流感病毒 肺炎 肺损伤

国家自然科学基金资助项目

31560292

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(3)
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