水蛭素对博莱霉素致特发性肺间质纤维化大鼠肺组织病理变化的影响
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摘要
目的:探讨水蛭素对博莱霉素致特发性肺间质纤维化大鼠肺组织病理变化的影响。方法:选取180只SPF级Wistar大鼠,随机抽取18只作为K组,剩余162只气管内推注博莱霉素统一造模,建模成功后随机选取108只分为M组、J组、G组、Z组、D组、ZJ组,每组各18只,建模成功后次日开始给药,给药的第7天、14天、28天分批处死大鼠后取右肺组织行HE、Masson染色,并计算肺组织病理损伤及肺纤维化评分。结果:通过比较不同组别不同时间点肺组织病理损伤和肺纤维化评分发现:与K组比较,各组大鼠肺组织纤维化评分在第7天、14天、28天均显著增高(P <0.01);其中M组大鼠评分均最高(P <0.01),ZJ组评分均最低(P <0.01),与G组相当(P> 0.05),且显著低于J组、Z组和D组(P> 0.05),而J组明显低于Z组和D组,Z组与D组相当(P> 0.05)。结论:水蛭素能不同程度地降低大鼠肺组织炎症反应,有抗纤维化的作用;G组与ZJ组水蛭素的治疗效果相当;水蛭素治疗效果有明显的剂量依赖性,与激素联用有协同作用。
Objective: To investigate efficacy of hirudin on the pathological changes of lung tissue in rats with idiopathic pulmonary fibrosis induced by bleomycin. Methods: 180 SPF Wistar rats were selected and 18 rats were randomly selected as the K group. The remaining 162 rats were made bleomycin by intratracheal drugs injections. After successful modeling, 108 rats were randomly selected into M group, J group and G group, Z group, D group, ZJ group, each group of 18 rats. The next day after the successful modeling, the rats were given drugs. After administered on the 7 th, 14 th, and 28 th days, the right lung tissue was taken for HE and Masson staining Lung tissue pathological damage and pulmonary fibrosis score were calculate. Results: By comparing the pathological damage and pulmonary fibrosis scores of lung tissue at different time points in different groups, the lung fibrosis scores of the rats in each group were significantly increased on the 7 th, 14 th and 28 th day(P<0.01). The scores of rats in M group were the highest(P<0.01), and those in ZJ group were the lowest(P<0.01), which was equivalent to G group(P>0.05), and significantly lower than J group, Z group and D group(P>0.05), while J group was significantly lower than Z group and D group, and Z group was comparable to D group(P>0.05). Conclusion: Hirudin can reduce the inflammatory reaction of rat lung tissue to different degrees, and has anti-fibrosis effect; G group and ZJ group have the same therapeutic effect; hirudin treatment has obvious dose-dependent effect, synergistic with hormone combination effect.
Objective: To investigate efficacy of hirudin on the pathological changes of lung tissue in rats with idiopathic pulmonary fibrosis induced by bleomycin. Methods: 180 SPF Wistar rats were selected and 18 rats were randomly selected as the K group. The remaining 162 rats were made bleomycin by intratracheal drugs injections. After successful modeling, 108 rats were randomly selected into M group, J group and G group, Z group, D group, ZJ group, each group of 18 rats. The next day after the successful modeling, the rats were given drugs. After administered on the 7 th, 14 th, and 28 th days, the right lung tissue was taken for HE and Masson staining Lung tissue pathological damage and pulmonary fibrosis score were calculate. Results: By comparing the pathological damage and pulmonary fibrosis scores of lung tissue at different time points in different groups, the lung fibrosis scores of the rats in each group were significantly increased on the 7 th, 14 th and 28 th day(P<0.01). The scores of rats in M group were the highest(P<0.01), and those in ZJ group were the lowest(P<0.01), which was equivalent to G group(P>0.05), and significantly lower than J group, Z group and D group(P>0.05), while J group was significantly lower than Z group and D group, and Z group was comparable to D group(P>0.05). Conclusion: Hirudin can reduce the inflammatory reaction of rat lung tissue to different degrees, and has anti-fibrosis effect; G group and ZJ group have the same therapeutic effect; hirudin treatment has obvious dose-dependent effect, synergistic with hormone combination effect.
引文
[1]周忠辉,骆仙芳.王会仍诊治肺间质纤维化经验[J].浙江中西医结合杂志,2018,28(05):343-345.
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[5]李晓娟,张骞云,蔡志刚,等.水蛭对肺纤维化大鼠羟脯氨酸、转化生长因子-β1及纤溶酶原激活物抑制因子-1的影响[J].安徽中医药大学学报,2013,32(03):57-61.
[6]李晓娟,张骞云,蔡志刚,等.水蛭对肺纤维化大鼠PAI-1的影响[J].贵阳医学院学报,2012,37(02):170-173.
[7]王志新,张志立,李哲诚,等.当归补血汤加味抗肝炎肝纤维化临床研究[J].亚太传统医药,2014,10(23):101-103.
[8]GUO F,SUN Y,SU L,et al.Losartan attenuates paraquatinduced pulmonary fibrosis in rats.[J].Human&Experimental Toxicology,2015,34(05):497-505.
[9]李伟峰,胡玉洁,袁伟锋,等.气管内滴入与雾化博莱霉素致小鼠肺纤维化模型的比较研究[J].南方医科大学学报,2012,32(02):221-225.
[10]Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits[J].Anesthesia&Analgesia,2003,97(06):1751.
[11]Selman M,Pardo A,Kaminski N.Idiopathic Pulmonary Fibrosis:Aberrant Recapitulation of Developmental Programs?[J].Plos Medicine,2008,5(03):e62.
[12]Fabre A,Marchal-SomméJ,Marchand-Adam S,et al.Modulation of bleomycin-induced lung fibrosis by seroton in receptor antagonists in mice[J].European Respiratory Journal,2008,32(02):426-436.
[13]Chaudhary N I,Park J E.Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model[J].American Journal of Respiratory&Critical Care Medicine,2006,173(07):769.
[14]周乐,赵文静,常惟智.水蛭的药理作用及临床应用研究进展[J].中医药信息,2012,29(01):132-133.
[15]李晶.水蛭的药理研究进展[J].科学技术创新,2012,16(30):33.
[16]李晓娟,张骞云,马洪霞,等.水蛭对肺纤维化大鼠的影响及机制探讨[J]中药药理与临床,2015,31(02):155-156.
[17]刘鑫洋,白林涛,姬菩宏,等.水蛭素研究进展[J].亚太传统医药,2017,13(16):50-52.
[18]郭睿,农晓琳,邓凌,等.水蛭素对皮肤增生性瘢痕成纤维细胞bFGF及TGFβ1表达的影响[J].中国美容医学,2011,20(04):614-617.
[19]郑燕林,王毅,武文忠,等.水蛭素对血小板源性生长因子及受体的影响[J].中华实验眼科杂志,2003,21(05):476-478.
[20]郑怡,禤坤,南澜,等.水蛭素对牙龈成纤维细胞碱性成纤维细胞生长因子和转化生长因子-β1表达的影响[J].华西口腔医学杂志,2015,33(01):6-10.
[21]梁桂文,姜敏辉.水蛭素对动脉内皮保护作用的实验研究[J].天津医药,2012,40(12):1234-1236.
[22]邢菲菲.分析HE染色技术在病理诊断中的应用[J].世界最新医学信息文摘,2017,17(31):8-9.
[23]林云恩,许惠娟,何萍,等.介绍一种Masson三色的微波改良染色法[J]实用医学杂志,2010,26(10):1865-1866.
[2]王海霞,李红,谢海彬,等.特发性肺间质纤维化的研究进展[J].中医临床研究,2017,9(30):9-12.
[3]王庆军.温阳化瘀法治疗特发性肺间质纤维化的临床研究[J].中国现代医生,2016,54(05):129-132.
[4]李晓娟.水蛭对大鼠肺纤维化模型干预作用及机制的研究[D].石家庄:河北医科大学,2007.
[5]李晓娟,张骞云,蔡志刚,等.水蛭对肺纤维化大鼠羟脯氨酸、转化生长因子-β1及纤溶酶原激活物抑制因子-1的影响[J].安徽中医药大学学报,2013,32(03):57-61.
[6]李晓娟,张骞云,蔡志刚,等.水蛭对肺纤维化大鼠PAI-1的影响[J].贵阳医学院学报,2012,37(02):170-173.
[7]王志新,张志立,李哲诚,等.当归补血汤加味抗肝炎肝纤维化临床研究[J].亚太传统医药,2014,10(23):101-103.
[8]GUO F,SUN Y,SU L,et al.Losartan attenuates paraquatinduced pulmonary fibrosis in rats.[J].Human&Experimental Toxicology,2015,34(05):497-505.
[9]李伟峰,胡玉洁,袁伟锋,等.气管内滴入与雾化博莱霉素致小鼠肺纤维化模型的比较研究[J].南方医科大学学报,2012,32(02):221-225.
[10]Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits[J].Anesthesia&Analgesia,2003,97(06):1751.
[11]Selman M,Pardo A,Kaminski N.Idiopathic Pulmonary Fibrosis:Aberrant Recapitulation of Developmental Programs?[J].Plos Medicine,2008,5(03):e62.
[12]Fabre A,Marchal-SomméJ,Marchand-Adam S,et al.Modulation of bleomycin-induced lung fibrosis by seroton in receptor antagonists in mice[J].European Respiratory Journal,2008,32(02):426-436.
[13]Chaudhary N I,Park J E.Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model[J].American Journal of Respiratory&Critical Care Medicine,2006,173(07):769.
[14]周乐,赵文静,常惟智.水蛭的药理作用及临床应用研究进展[J].中医药信息,2012,29(01):132-133.
[15]李晶.水蛭的药理研究进展[J].科学技术创新,2012,16(30):33.
[16]李晓娟,张骞云,马洪霞,等.水蛭对肺纤维化大鼠的影响及机制探讨[J]中药药理与临床,2015,31(02):155-156.
[17]刘鑫洋,白林涛,姬菩宏,等.水蛭素研究进展[J].亚太传统医药,2017,13(16):50-52.
[18]郭睿,农晓琳,邓凌,等.水蛭素对皮肤增生性瘢痕成纤维细胞bFGF及TGFβ1表达的影响[J].中国美容医学,2011,20(04):614-617.
[19]郑燕林,王毅,武文忠,等.水蛭素对血小板源性生长因子及受体的影响[J].中华实验眼科杂志,2003,21(05):476-478.
[20]郑怡,禤坤,南澜,等.水蛭素对牙龈成纤维细胞碱性成纤维细胞生长因子和转化生长因子-β1表达的影响[J].华西口腔医学杂志,2015,33(01):6-10.
[21]梁桂文,姜敏辉.水蛭素对动脉内皮保护作用的实验研究[J].天津医药,2012,40(12):1234-1236.
[22]邢菲菲.分析HE染色技术在病理诊断中的应用[J].世界最新医学信息文摘,2017,17(31):8-9.
[23]林云恩,许惠娟,何萍,等.介绍一种Masson三色的微波改良染色法[J]实用医学杂志,2010,26(10):1865-1866.