基于信号通路p38 MAPK探讨疏风宣肺汤对大鼠慢性支气管炎模型TNF-α的影响
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摘要
目的观察疏风宣肺汤对慢性支气管炎大鼠血清以及肺组织中肿瘤坏死因子(tumor nercrosis factor-α, TNF-α)的影响。方法将60只SPF级大鼠,随机分为空白组、生理盐水组、宣肺止咳合剂组和疏风宣肺汤组,每组15只;空白组正常饲养,余组采用脂多糖-香烟烟雾诱导法造模成功后分别予以生理盐水、宣肺止咳合剂、疏风宣肺汤灌胃,1周后行腹主动脉采血,剪下右肺,检测血清中TNF-α浓度,肺组织中TNF-αmRNA、TNF-α蛋白以及p-p38 MAPK蛋白的表达。结果在药物干预7 d后,各组大鼠血清中TNF-α浓度以及肺组织中的TNF-αmRNA、TNF-α蛋白、p-p38 MAPK蛋白的表达差异性均有统计学意义(P<0.05)。与空白组相比,疏风宣肺汤组,生理盐水组、宣肺止咳合剂组中各检测指标差异有统计学意义(P<0.05);与生理盐水组相比,疏风宣肺汤组和宣肺止咳含剂组差异有显著性统计学意义(P<0.01或P<0.05)。结论疏风宣肺汤能显著降低慢支大鼠血清中TNF-α浓度以及肺组织TNF-αmRNA、TNF-α蛋白、p-p38 MAPK蛋白表达,减少p38 MAPK信号通路的活化可能是疏风宣肺汤有效防治慢性支气管炎的机制之一。
Objective To observe the effects of Shufeng Xuanfei Decoction on tumor nercrosis factor-α(TNF-α) in serum and lung tissue of rats with chronic bronchitis. Methods A total of 60 SPF rats were randomly divided into a blank group,a normal saline group, a Xuanfei Zhike Mixture group and a Shufeng Xuanfei Decoction group, with 15 rats in each group. The blank group was fed normally, while the rest groups were given with normal saline, Xuanfei Zhike Mixture and Shufeng Xuanfei Decoction after successful modeling by lipopolysaccharide-cigarette smoke induction method. After 1 week, blood was collected from the abdominal aorta, the right lung was cut off, and the concentration of TNF-α in serum and the expressions of TNF-α mRNA, TNF-α protein and p-p38 MAPK protein in lung tissue were detected. Results After 7 d of medical intervention,the differences in the concentration of TNF-α in serum and the expressions of TNF-α mRNA, TNF-α protein and p-p38 MAPK protein in lung tissue of rats in each group were statistically significant(P<0.05). Furthermore, compared with the blank group,the differences of indexes in the Shufeng Xuanfei Decoction group, the normal saline group and the Xuanfei Zhike Mixture group were statistically significant(P<0.05). Compared with the normal saline group, the difference in the Shufeng Xuanfei Decoction group and the Xuanfei Zhike Mixture group was statistically significant(P<0.01 or P<0.05). Conclusion Shufeng Xuanfei Decoction can significantly reduce the concentration of TNF-α in serum of rats with chronic bronchitis and the expressions of TNF-α mRNA,TNF-α protein and p-p38 MAPK protein in lung tissue. Reducing the activation of p38 MAPK signaling pathway may be one of the effective mechanisms for preventing and treating chronic bronchitis by Shufeng Xuanfei Decoction.
Objective To observe the effects of Shufeng Xuanfei Decoction on tumor nercrosis factor-α(TNF-α) in serum and lung tissue of rats with chronic bronchitis. Methods A total of 60 SPF rats were randomly divided into a blank group,a normal saline group, a Xuanfei Zhike Mixture group and a Shufeng Xuanfei Decoction group, with 15 rats in each group. The blank group was fed normally, while the rest groups were given with normal saline, Xuanfei Zhike Mixture and Shufeng Xuanfei Decoction after successful modeling by lipopolysaccharide-cigarette smoke induction method. After 1 week, blood was collected from the abdominal aorta, the right lung was cut off, and the concentration of TNF-α in serum and the expressions of TNF-α mRNA, TNF-α protein and p-p38 MAPK protein in lung tissue were detected. Results After 7 d of medical intervention,the differences in the concentration of TNF-α in serum and the expressions of TNF-α mRNA, TNF-α protein and p-p38 MAPK protein in lung tissue of rats in each group were statistically significant(P<0.05). Furthermore, compared with the blank group,the differences of indexes in the Shufeng Xuanfei Decoction group, the normal saline group and the Xuanfei Zhike Mixture group were statistically significant(P<0.05). Compared with the normal saline group, the difference in the Shufeng Xuanfei Decoction group and the Xuanfei Zhike Mixture group was statistically significant(P<0.01 or P<0.05). Conclusion Shufeng Xuanfei Decoction can significantly reduce the concentration of TNF-α in serum of rats with chronic bronchitis and the expressions of TNF-α mRNA,TNF-α protein and p-p38 MAPK protein in lung tissue. Reducing the activation of p38 MAPK signaling pathway may be one of the effective mechanisms for preventing and treating chronic bronchitis by Shufeng Xuanfei Decoction.
引文
[1]葛均波,徐永健.内科学[M].8版.北京:人民卫生出版社,2013:19-19.
[2]淦克职.中医治疗慢性支气管炎肺气肿63例[J].中国中医药现代远程教育,2016,14(8):90-92.
[3]甘学军,汪小华,胡刚.慢性支气管炎急性发作期患者血清肿瘤坏死因子α、白介素6水平变化及其临床意义[J].实用心脑肺血管病杂志,2016,24(5):127-12.
[4]程越,邱志新,李为民.慢性支气管炎发病机制研究进展[J].华西医学,2017,32(4):606-611.
[5]张金波,王新陆,孙丽,等.清肺化浊行血宽中方对PM2.5引起慢性支气管炎大鼠肺组织病理学及血清IL-8、TNF-α的影响[J].中华全科医学,2017,15(12):2028-2031.
[6]欧阳金生.脂多糖—烟雾诱导慢性支气管炎大鼠模型水通道蛋白5表达与肿瘤坏死因子α、白介素13、白三烯B4的变化[D].厦门:福建医科大学,2006:34-37.
[7]徐杰.宣肺止咳颗粒的药效学研究[J].中国民族民间医药,2011,15:37-38.
[8]周晓霞,程敏,杨琳,等.宣肺止咳合剂抗小鼠肺组织损伤及NO水平的研究[J].中华中医药学刊,2014,32(5):1096-1098.
[9]李军.蜕皮甾酮对急性肺损伤大鼠肺组织中TNF-αm RNA及SP-A表达的影响[D].广州:南方医科大学,2013.
[10]蒋叶,吕伟,余书勤,等.艾拉莫德对脂多糖激活大鼠肺泡巨噬细胞系TNF-α产生及NF-κB活性的抑制作用[J].药学学报,2006,41(5):401-405.
[11]彭先祝.止咳平喘软胶囊治疗慢性妨詹炎急性发作期的临床观察及对血清一的影响从而造成支气管肺组织的损伤[D].黑龙江中医药大学,2011:17-19.
[12]闵锐.疏风宣肺汤治疗单纯型慢性支气管炎迁延期风邪伏肺证的临床观察[D].长沙:湖南中医药大学,2017:12-13.
[13]王志超,李晶.从风论治咳嗽变异性哮喘[J].世界中西医结合杂志,2018,13(2):289-291.
[14]梅全喜.现代中药药理[M].北京:中国中医出版社,2016:43-72.
[15] HUANG C, J ACOBSON K, SCHALLER M D. MAP kinase and cell migration[J]. Journal of Cell Science, 2004,117(20):4619-4628.
[16] LILIA SC, VALERIE F, FRANCO P, et al. Dual effects of P38MAPK on tnf-depende bronchoconst riction and tnf-independent neut rophil recruitment in lipopolysaccharide.induced acute respirato ry dist ress syndrome[J]. Journal of Immunology,2005,175(1):262-269.
[17]吕小琴.p38 MAPK特异性抑制剂SB 239063[J].国外医学(呼吸系统分册),2004(1):38-39.
[18] SNVEGNAGO L. PINTO I G, JESSE C R, et al. Spinal mechanisms of antinociceptive action caused by diphenyl diselenide[J].Brain Research, 2007,116(2):32-37.
[19] SVENSSON C L, SCHAFER M, JONES T L, et al. Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal p-p38[J]. Neuroscience Letters, 2005,379(3):209-213.
[20]丛培玮.肺气虚模型大鼠介导TNF-α/p38MAPK信号转导途径对肾组织AQPs表达影响[D].沈阳:辽宁中医药大学,2012:31-32.
[21]李原青,李逊.加减补肺汤对肺气虚证大鼠血清及含量变化的影响[J].江西中医药,2004,8(35):57-58.
[22]陈永兰.p38 MAPK信号通路对小胶质细胞功能及NGF、TNF-α分泌的影响[D].大连:大连医科大学,2012.
[23]程越,邱志新,李为民,等.慢性支气管炎发病机制研究进展[J],华西医学,2017,4(32):606-611.
[24]孙希.基于P38MAPK探讨隔药饼灸对慢性支气管炎模型大鼠肺组织TNF-α的影响及作用机理[D].长沙:湖南中医药大学,2013.
[2]淦克职.中医治疗慢性支气管炎肺气肿63例[J].中国中医药现代远程教育,2016,14(8):90-92.
[3]甘学军,汪小华,胡刚.慢性支气管炎急性发作期患者血清肿瘤坏死因子α、白介素6水平变化及其临床意义[J].实用心脑肺血管病杂志,2016,24(5):127-12.
[4]程越,邱志新,李为民.慢性支气管炎发病机制研究进展[J].华西医学,2017,32(4):606-611.
[5]张金波,王新陆,孙丽,等.清肺化浊行血宽中方对PM2.5引起慢性支气管炎大鼠肺组织病理学及血清IL-8、TNF-α的影响[J].中华全科医学,2017,15(12):2028-2031.
[6]欧阳金生.脂多糖—烟雾诱导慢性支气管炎大鼠模型水通道蛋白5表达与肿瘤坏死因子α、白介素13、白三烯B4的变化[D].厦门:福建医科大学,2006:34-37.
[7]徐杰.宣肺止咳颗粒的药效学研究[J].中国民族民间医药,2011,15:37-38.
[8]周晓霞,程敏,杨琳,等.宣肺止咳合剂抗小鼠肺组织损伤及NO水平的研究[J].中华中医药学刊,2014,32(5):1096-1098.
[9]李军.蜕皮甾酮对急性肺损伤大鼠肺组织中TNF-αm RNA及SP-A表达的影响[D].广州:南方医科大学,2013.
[10]蒋叶,吕伟,余书勤,等.艾拉莫德对脂多糖激活大鼠肺泡巨噬细胞系TNF-α产生及NF-κB活性的抑制作用[J].药学学报,2006,41(5):401-405.
[11]彭先祝.止咳平喘软胶囊治疗慢性妨詹炎急性发作期的临床观察及对血清一的影响从而造成支气管肺组织的损伤[D].黑龙江中医药大学,2011:17-19.
[12]闵锐.疏风宣肺汤治疗单纯型慢性支气管炎迁延期风邪伏肺证的临床观察[D].长沙:湖南中医药大学,2017:12-13.
[13]王志超,李晶.从风论治咳嗽变异性哮喘[J].世界中西医结合杂志,2018,13(2):289-291.
[14]梅全喜.现代中药药理[M].北京:中国中医出版社,2016:43-72.
[15] HUANG C, J ACOBSON K, SCHALLER M D. MAP kinase and cell migration[J]. Journal of Cell Science, 2004,117(20):4619-4628.
[16] LILIA SC, VALERIE F, FRANCO P, et al. Dual effects of P38MAPK on tnf-depende bronchoconst riction and tnf-independent neut rophil recruitment in lipopolysaccharide.induced acute respirato ry dist ress syndrome[J]. Journal of Immunology,2005,175(1):262-269.
[17]吕小琴.p38 MAPK特异性抑制剂SB 239063[J].国外医学(呼吸系统分册),2004(1):38-39.
[18] SNVEGNAGO L. PINTO I G, JESSE C R, et al. Spinal mechanisms of antinociceptive action caused by diphenyl diselenide[J].Brain Research, 2007,116(2):32-37.
[19] SVENSSON C L, SCHAFER M, JONES T L, et al. Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal p-p38[J]. Neuroscience Letters, 2005,379(3):209-213.
[20]丛培玮.肺气虚模型大鼠介导TNF-α/p38MAPK信号转导途径对肾组织AQPs表达影响[D].沈阳:辽宁中医药大学,2012:31-32.
[21]李原青,李逊.加减补肺汤对肺气虚证大鼠血清及含量变化的影响[J].江西中医药,2004,8(35):57-58.
[22]陈永兰.p38 MAPK信号通路对小胶质细胞功能及NGF、TNF-α分泌的影响[D].大连:大连医科大学,2012.
[23]程越,邱志新,李为民,等.慢性支气管炎发病机制研究进展[J],华西医学,2017,4(32):606-611.
[24]孙希.基于P38MAPK探讨隔药饼灸对慢性支气管炎模型大鼠肺组织TNF-α的影响及作用机理[D].长沙:湖南中医药大学,2013.