基于NRG/ErbB 信号通路探讨紫草素对哮喘模型大鼠的影响
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R285.5

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Shikonin Has Effect on Rat Models with Asthma Based on NRG/ErbB Signaling Path⁃ways
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    摘要:

    目的:基于神经调节蛋白/表皮生长因子受体(NRG/ErbB) 信号通路探讨紫草素对哮喘模型大鼠的影响。方法:将100 只SPF 级Wistar 大鼠根据体质量随机分成对照组、模型组、地塞米松组、紫草素低、高剂量组5 组。模型组、地塞米松组、紫草素低、高剂量组大鼠构建哮喘模型,模型制备成功后,地塞米松组、紫草素低、高剂量组给予相应药物灌胃;对照组及模型组给予相应体积的生理盐水。测定湿肺/体质量、血氧分压(PaO2),并对肺组织进行常规染色切片,行肺损伤评分,RT-PCR与免疫组织化学法分别测定肺组织中NRG、ErbB mRNA 和蛋白水平,ELISA 法测定肺组织白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α) 水平。结果:与对照组比较,模型组湿肺/体质量比值、肺损伤评分、淋巴细胞、嗜酸性粒细胞、中性粒细胞水平、肺NRG、ErbB mRNA 和蛋白表达水平、IL-2、IL-6、TNF-α 蛋白表达水平均明显升高(P<0.05);PaO2水平明显降低(P<0.05)。与模型组比较,地塞米松组、紫草素低、高剂量组湿肺/体质量比值、肺损伤评分、淋巴细胞、嗜酸性粒细胞、中性粒细胞水平、肺NRG、ErbB mRNA 和蛋白表达水平、IL-2、IL-6、TNF-α 蛋白表达水平明显降低(P<0.05),PaO2水平明显升高(P<0.05);且紫草素高剂量组湿肺/体质量、肺损伤评分、淋巴细胞、嗜酸性粒细胞、中性粒细胞水平、肺NRG、ErbB mRNA 和蛋白表达水平、IL-2、IL-6、TNF-α 蛋白表达水平较低剂量组低(P<0.05),PaO2水平较低剂量组高(P<0.05)。与地塞米松组比较,紫草素低剂量组湿肺/体质量比值、肺损伤评分、淋巴细胞、嗜酸性粒细胞、中性粒细胞水平、肺NRG、ErbB mRNA 及蛋白表达水平、IL-2、IL-6、TNF-α 蛋白表达水平明显升高(P<0.05),PaO2水平明显降低(P<0.05),而紫草素高剂量组上述指标比较,差异无统计学意义(P>0.05)。结论:紫草素能明显降低哮喘模型大鼠肺部过敏性炎症反应,高剂量的紫草素与地塞米松有相似的效果;且其作用机制与紫草素抑制NRG、ErbB mRNA和蛋白表达水平进而抑制细胞炎症因子IL-2、IL-6、TNF-α水平有关。

    Abstract:

    Abstract:Objective:Based on neuregulin/epidermal growth factor receptor(NRG/ErbB) signaling pathways,to discuss the effect of shikonin on rat models with asthma. Methods:A total of 100 SPF Wistar rats were randomly divided into the control group,the model group,the dexamethasone group and the shikonin group of low-dose and high-dose according to their body mass. Rat models with asthma were established in the model group,the dexamethasone group and the shikonin group of low-dose and high-dose,and then were given gastric perfusion correspondingly. The control group and the model group were given saline of corresponding volume. The ratio of wet lung and body mass and partial pressure of oxygen(PaO2) were measured;the lung tissues were sectioned and stained routinely;the lung injury was scored;the expression levels of mRNA and protein of NRG and ErbB in the lung tissues were measured by RT-PCR and immunohistochemistry respectively;the levels of interleukin-2(IL-2),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the lung tissues were measured by ELISA method. Results:Compared with those in the control group,the ratio of wet lung and body mass,the score of lung injury, the levels of lymphocyte, eosinophil and neutrophil, the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL-2,IL-6 and TNF-α in the model group were significantly increased (P<0.05);the level of PaO2 was significantly decreased(P<0.05). Compared with those in the model group,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung, and the protein expression levels of IL- 2, IL- 6 and TNF- α in the dexamethasone group and the shikonin group of low-dose and high-dose were significantly decreased(P<0.05);the levels of PaO2 were significantly increased(P<0.05). Compared with the shikonin groud of low-dose,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL- 2,IL-6 and TNF-α in the shikonin groud of high- dose were decreased(P<0.05),and the level of PaO2 was increased(P<0.05). Compared with those in the dexamethasone group,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL-2,IL-6 and TNF-α in the shikonin group of low-dose were significantly increased(P<0.05),and the level of PaO2 was significantly decreased(P<0.05). There was no significant difference being found in the comparison of the above indexes between the dexamethasone group and the shikonin group of high- dose(P > 0.05). Conclusion: Shikonin can significantly decrease allergic inflammatory responses in the rat models with asthma, and high- dose shikonin has similar effect to dexamethasone. The mechanism of shikonin is related to its inhibition on the levels of inflammatory factors including IL- 2,IL-6 and TNF-α by inhibiting the expression levels of mRNA and protein of NRG and ErbB.

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郑静,陈锋,徐婷婷,王万勇.基于NRG/ErbB 信号通路探讨紫草素对哮喘模型大鼠的影响[J].新中医,2020,52(10):4-8

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  • 在线发布日期: 2020-05-26
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