淫羊藿苷及宝藿苷Ⅰ对气管切开模型大鼠肺组织病理学及炎症因子的影响
|
摘要
目的探讨淫羊藿苷及其代谢产物宝藿苷Ⅰ对气管切开模型大鼠肺组织病理及炎症的影响。方法将72只SPF级雄性SD大鼠随机分成四组,正常对照组(A)、模型非用药组(B)、模型+宝藿苷I组(C)、模型+淫羊藿苷组(D),每组18只。制备大鼠气管切开插管留置模型。模型成功6 h后给予C组宝藿苷I,D组淫羊藿苷干预,A、B组给与等量0. 9%生理盐水。分别在24、72、168 h取肺组织及肺泡灌洗液。肺组织用苏木精-伊红染色(HE染色),光镜下观察分析肺组织的病理学改变; ELISA检测肺泡灌洗液白细胞介素6(IL-6),肿瘤坏死因子α(TNF-α)表达。结果 1)肺组织病理结果显示:气管切开后B组大鼠肺损伤程度随时间延长逐渐加重,明显高于A组(P<0. 05)。C、D组肺损伤程度均明显轻于B组,且D组在24、168 h均明显轻于C组(P<0. 05)。D组在168h病理评分明显降低(与24 h比较P<0. 01)。(2)肺泡灌洗液IL-6、TNF-α含量:气管切开插管后大鼠肺泡灌洗液IL-6和TNF-α含量在三个时段均明显高于A组(P<0. 05)。用宝藿苷I和淫羊藿苷干预后,C、D组IL-6、TNF-α含量在72、168 h明显低于B组(P<0. 05);且C、D组组内IL-6和TNF-α含量在72、168 h明显低于24 h(P<0. 05); D组与C组相比,IL-6含量无明显统计学差异(P> 0. 05)。D组TNF-α在72 h、168 h均明显低于C(P<0. 05)。结论宝藿苷I和淫羊藿苷对气管切开术后早期肺部炎症有一定疗效,其机制与抑制肺泡灌洗液炎症因子IL-6、TNF-α的表达,减轻肺组织损伤有关,且淫羊藿苷效果更佳。
Objective To investigate the effects of icariin and its metabolite,baohuoside I,on the pathology and inflammation of lung tissue in tracheotomized rats. Methods Seventy-two SPF male Sprague-Dawley rats were randomly divided into four groups: normal control group( A),model control group( B),and model treatment group( C and D) with18 rats in each group. A rat tracheotomy tube indwelling model was established. At 6 hours after successful modeling,the groups C and D were administered icariin and baohuoside I,respectively. The groups A and B were administered an equal amount of 0. 9% normal saline. Lung tissue and alveolar lavage fluid were collected at 24,72,and 168 h. Pathological examination of the lung tissues was performed using HE staining. ELISA was used to detect the interleukin-6( IL-6) and tumor necrosis factor alpha( TNF-α) in alveolar lavage fluid. Results After the tracheotomy,the degree of histological changes in the lung tissues of the group B was gradually increased over time,significantly higher than that in the group A( P < 0. 05). The degree of lung injury in the groups C and D was significantly lower than that in the group B,and that in the group D was significantly lower compared with the group C at 24 and 168 h after tracheotomy( P < 0. 05). The pathological score of group D was significantly lower at 168 h( P < 0. 01 compared with 24 h). The contents of IL-6 and TNF-α in alveolar lavage fluid of the rats after tracheotomy were significantly higher than those in the group A( P < 0. 05).After treatments with baohuoside I and icariin,the levels of IL-6 and TNF-α in the groups C and D were significantly lower than those in the group B at 72 and 168 h( P<0. 05),and the IL-6 and TNF-α contents in the groups C and D at 72 h and168 h were significantly lower than that after 24 h( P<0. 05). There was no significant difference in the IL-6 contents of groups C and D at 72 h and 168 h( P > 0. 05). TNF-α contents in the group D at 72 and 168 h were significantly lower than that in the group C( P < 0. 05). Conclusions Baohuoside I and icariin have certain therapeutic effects on the early lung inflammation after tracheotomy. The mechanism is related to inhibiting the release of inflammatory factors IL-6 and TNF-α into alveolar lavage fluid and alleviating lung tissue damage. Moreover,the effect of icariin is better than that of baohuoside I.
Objective To investigate the effects of icariin and its metabolite,baohuoside I,on the pathology and inflammation of lung tissue in tracheotomized rats. Methods Seventy-two SPF male Sprague-Dawley rats were randomly divided into four groups: normal control group( A),model control group( B),and model treatment group( C and D) with18 rats in each group. A rat tracheotomy tube indwelling model was established. At 6 hours after successful modeling,the groups C and D were administered icariin and baohuoside I,respectively. The groups A and B were administered an equal amount of 0. 9% normal saline. Lung tissue and alveolar lavage fluid were collected at 24,72,and 168 h. Pathological examination of the lung tissues was performed using HE staining. ELISA was used to detect the interleukin-6( IL-6) and tumor necrosis factor alpha( TNF-α) in alveolar lavage fluid. Results After the tracheotomy,the degree of histological changes in the lung tissues of the group B was gradually increased over time,significantly higher than that in the group A( P < 0. 05). The degree of lung injury in the groups C and D was significantly lower than that in the group B,and that in the group D was significantly lower compared with the group C at 24 and 168 h after tracheotomy( P < 0. 05). The pathological score of group D was significantly lower at 168 h( P < 0. 01 compared with 24 h). The contents of IL-6 and TNF-α in alveolar lavage fluid of the rats after tracheotomy were significantly higher than those in the group A( P < 0. 05).After treatments with baohuoside I and icariin,the levels of IL-6 and TNF-α in the groups C and D were significantly lower than those in the group B at 72 and 168 h( P<0. 05),and the IL-6 and TNF-α contents in the groups C and D at 72 h and168 h were significantly lower than that after 24 h( P<0. 05). There was no significant difference in the IL-6 contents of groups C and D at 72 h and 168 h( P > 0. 05). TNF-α contents in the group D at 72 and 168 h were significantly lower than that in the group C( P < 0. 05). Conclusions Baohuoside I and icariin have certain therapeutic effects on the early lung inflammation after tracheotomy. The mechanism is related to inhibiting the release of inflammatory factors IL-6 and TNF-α into alveolar lavage fluid and alleviating lung tissue damage. Moreover,the effect of icariin is better than that of baohuoside I.
引文
[1] Shay S,Shapiro NL,Bhattacharyya N. Revisits after pediatric tracheotomy:Airway concerns result in returns[J]. Int J Pediatr Otorhinolaryngol,2018,104:5-9.
[2] Russell CJ, Thurm C, Hall M, et al. Risk factors for hospitalizations due to bacterial respiratory tract infections after tracheotomy[J]. Pediatr Pulmonol,2018,53(3):349-357.
[3]朱翠香,彭玲玲,潘宇政,等.淫羊藿对气管切开插管留置大鼠免疫功能的影响[J].广西医学,2018,40(07):803-807.Zhu CX,Peng LL,Pan YZ,et al. The effects of Epimedium polysaccharides on pulmonary immune function in rats with tracheostomy[J]. Guangxi Med J,2018,40(07):803-807.
[4] Zhai YK,Guo X,Pan YL,et al. A systematic review of the efficacy and pharmacological profile of herba epimedii in osteoporosis therapy[J]. Pharmazie,2013,68(9):713-722.
[5] Gui Y,Zhang J,Chen L,et al. Icariin,a flavonoid with anticancer effects,alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner[J]. Mol Pain, 2018,14:1744806918768970.
[6] Gandhi GR,Neta MTSL,Sathiyabama R G,et al. Flavonoids as Th1/Th2 cytokines immunomodulators:A systematic review of studies on animal models[J]. Phytomedicine,2018,44:74-84.
[7] Shi Y, Yan W, Lin Q, et al. Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway[J]. J Int Med Res,2018,46(6):2371-2385.
[8]朱翠香,彭玲玲,张冉令,等.一次性硬膜外麻醉导管气管切开插管留置大鼠模型的建立[J].中华实验外科杂志,2015,32(10):2480.Zhu XC,Peng LL,Zhang RL,et al. Establishment of a rat model of tracheotomy and intubation in a disposable epidural anesthesia catheter[J].Chin J Exp Surg,2015,32(10):2480.
[9]徐叔云,卞如濂,陈修.药理实验方法学-3版[M].人民卫生出版社,2002:202-204.Xu SY, Bian RL, Chen X. Pharmacological Experimental Methodology-3rd Edition[M]. Beijing,People’s Medical Publishing House,2002:202-204.
[10]李丽玮,花紫菱,张惠箴,等.输血相关急性肺损伤大鼠模型建立及肺组织病理研究[J].中国输血杂志,2012,25(11):1121-1124.Li LW, Hua ZL, Zhang HJ, et al. Pulmonary pathological changes in a rat model of transfusion-related acute lung injury[J]. Chin J Blood Transfus,2012,25(11):1121-1124.
[11]漆冬梅.温肾补肺化痰法治疗慢性阻塞性肺疾病稳定期160例临床观察[J].中医临床研究,2014,6(23):44-45.Qi DM. Clinical observation on treating 160 cases of obstructive pulmonary diseases in slationary phase by the Wenshen Bufei huatan therapy[J]. Clin Res Tradit Chin Med,2014,6(23):44-45.
[12] Wang G,Liu B,Cao Y,et al. Effects of two Chinese herbal formula for the treatment of moderate to severe stable chronic obstructive pulmonary disease:a multicenter, doubleblind,randomized controlled trial[J]]. PLoS One, 2014, 9(8):e103168.
[13] Qiao J,Sun S,Yuan L,et al. Effects of icariin on asthma mouse model are associated with regulation of prostaglandin D2 level[J]. Allergol Immunopathol,2017,45(6):567-572.
[14] Hunter CA,Jones SA. IL-6 as a keystone cytokine in health and disease[J]. Nat Immunol,2015,16(5):448-457.
[15] Wang HT,Fang YQ,Bao XC,et al. Expression changes of TNF-α,IL-1βand IL-6 in the rat lung of decompression sickness induced by fast buoyancy ascent escape[J]. Undersea Hyperb Med,2015,42(1):23-31.
[16] Redente EF,Keith RC,Janssen W,et al. Tumor necrosis factor-αaccelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages[J]. Am J Respir Cell Mol Biol,2014,50(4):825-837.
[17]洪原城,洪林杰,黄种杰,等.血清NT-proBNP、IL-6、TNF-α检测在肺损伤病情与预后评估中的应用价值[J].国际检验医学杂志,2017,38(12):1603-1605.Hong YC,Hong LJ,Huang ZJ,et al. The value of serum NTproBNP,IL-6 and TNF-αin evaluation of severity and prognosis of lung injury[J]. Int J Lab Med,2017,38(12):1603-1605.
[18]魏珍星,范崇盛,薛柯凡,等.耳鼻喉术后并发感染患者的血清炎症因子、T淋巴细胞亚群表达及临床意义研究[J].中华医院感染学杂志,2017,27(02):396-398.Wei ZX, Fan CS, Xue KF, et al. Expression of serum inflammatory cytokines,T lymphocyte subsets in ENT surgery patients complicated with postoperative infections and its clinical significance[J]. Chin J Nosocomiol,2017,27(02):396-398.
[19] Ma H,He X,Yang Y,et al. The genus Epimedium:An ethnopharmacological and phytochemical review[J]. J Ethnopharmacol,2011,134(3):519-541.
[20]刘蕊,赵健蕾,孙晓东,等.中药淫羊藿调控肝脏脂代谢功能初探[J].中药药理与临床,2018,34(01):92-96.Liu R, Zhao JL, Sun XD, et al. To explore the effect of Epimedium on lipid metabolism[J]. Pharmacol Clin Chin Mat Med,2018,34(01):92-96.
[21] Cheng T, Zhang Y, Zhang T, et al. Comparative pharmacokinetics study of icariin and icariside II in rats[J].Molecules,2015,20(12):21274-21286.
[2] Russell CJ, Thurm C, Hall M, et al. Risk factors for hospitalizations due to bacterial respiratory tract infections after tracheotomy[J]. Pediatr Pulmonol,2018,53(3):349-357.
[3]朱翠香,彭玲玲,潘宇政,等.淫羊藿对气管切开插管留置大鼠免疫功能的影响[J].广西医学,2018,40(07):803-807.Zhu CX,Peng LL,Pan YZ,et al. The effects of Epimedium polysaccharides on pulmonary immune function in rats with tracheostomy[J]. Guangxi Med J,2018,40(07):803-807.
[4] Zhai YK,Guo X,Pan YL,et al. A systematic review of the efficacy and pharmacological profile of herba epimedii in osteoporosis therapy[J]. Pharmazie,2013,68(9):713-722.
[5] Gui Y,Zhang J,Chen L,et al. Icariin,a flavonoid with anticancer effects,alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner[J]. Mol Pain, 2018,14:1744806918768970.
[6] Gandhi GR,Neta MTSL,Sathiyabama R G,et al. Flavonoids as Th1/Th2 cytokines immunomodulators:A systematic review of studies on animal models[J]. Phytomedicine,2018,44:74-84.
[7] Shi Y, Yan W, Lin Q, et al. Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway[J]. J Int Med Res,2018,46(6):2371-2385.
[8]朱翠香,彭玲玲,张冉令,等.一次性硬膜外麻醉导管气管切开插管留置大鼠模型的建立[J].中华实验外科杂志,2015,32(10):2480.Zhu XC,Peng LL,Zhang RL,et al. Establishment of a rat model of tracheotomy and intubation in a disposable epidural anesthesia catheter[J].Chin J Exp Surg,2015,32(10):2480.
[9]徐叔云,卞如濂,陈修.药理实验方法学-3版[M].人民卫生出版社,2002:202-204.Xu SY, Bian RL, Chen X. Pharmacological Experimental Methodology-3rd Edition[M]. Beijing,People’s Medical Publishing House,2002:202-204.
[10]李丽玮,花紫菱,张惠箴,等.输血相关急性肺损伤大鼠模型建立及肺组织病理研究[J].中国输血杂志,2012,25(11):1121-1124.Li LW, Hua ZL, Zhang HJ, et al. Pulmonary pathological changes in a rat model of transfusion-related acute lung injury[J]. Chin J Blood Transfus,2012,25(11):1121-1124.
[11]漆冬梅.温肾补肺化痰法治疗慢性阻塞性肺疾病稳定期160例临床观察[J].中医临床研究,2014,6(23):44-45.Qi DM. Clinical observation on treating 160 cases of obstructive pulmonary diseases in slationary phase by the Wenshen Bufei huatan therapy[J]. Clin Res Tradit Chin Med,2014,6(23):44-45.
[12] Wang G,Liu B,Cao Y,et al. Effects of two Chinese herbal formula for the treatment of moderate to severe stable chronic obstructive pulmonary disease:a multicenter, doubleblind,randomized controlled trial[J]]. PLoS One, 2014, 9(8):e103168.
[13] Qiao J,Sun S,Yuan L,et al. Effects of icariin on asthma mouse model are associated with regulation of prostaglandin D2 level[J]. Allergol Immunopathol,2017,45(6):567-572.
[14] Hunter CA,Jones SA. IL-6 as a keystone cytokine in health and disease[J]. Nat Immunol,2015,16(5):448-457.
[15] Wang HT,Fang YQ,Bao XC,et al. Expression changes of TNF-α,IL-1βand IL-6 in the rat lung of decompression sickness induced by fast buoyancy ascent escape[J]. Undersea Hyperb Med,2015,42(1):23-31.
[16] Redente EF,Keith RC,Janssen W,et al. Tumor necrosis factor-αaccelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages[J]. Am J Respir Cell Mol Biol,2014,50(4):825-837.
[17]洪原城,洪林杰,黄种杰,等.血清NT-proBNP、IL-6、TNF-α检测在肺损伤病情与预后评估中的应用价值[J].国际检验医学杂志,2017,38(12):1603-1605.Hong YC,Hong LJ,Huang ZJ,et al. The value of serum NTproBNP,IL-6 and TNF-αin evaluation of severity and prognosis of lung injury[J]. Int J Lab Med,2017,38(12):1603-1605.
[18]魏珍星,范崇盛,薛柯凡,等.耳鼻喉术后并发感染患者的血清炎症因子、T淋巴细胞亚群表达及临床意义研究[J].中华医院感染学杂志,2017,27(02):396-398.Wei ZX, Fan CS, Xue KF, et al. Expression of serum inflammatory cytokines,T lymphocyte subsets in ENT surgery patients complicated with postoperative infections and its clinical significance[J]. Chin J Nosocomiol,2017,27(02):396-398.
[19] Ma H,He X,Yang Y,et al. The genus Epimedium:An ethnopharmacological and phytochemical review[J]. J Ethnopharmacol,2011,134(3):519-541.
[20]刘蕊,赵健蕾,孙晓东,等.中药淫羊藿调控肝脏脂代谢功能初探[J].中药药理与临床,2018,34(01):92-96.Liu R, Zhao JL, Sun XD, et al. To explore the effect of Epimedium on lipid metabolism[J]. Pharmacol Clin Chin Mat Med,2018,34(01):92-96.
[21] Cheng T, Zhang Y, Zhang T, et al. Comparative pharmacokinetics study of icariin and icariside II in rats[J].Molecules,2015,20(12):21274-21286.