苦参颗粒对兔耳痤疮模型P38MAPK/ERK相关信号通路的影响
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摘要
目的:探讨苦参颗粒溶液对兔耳痤疮模型P38MAPK/ERK相关信号通路的影响及其治疗效果。方法:家兔除空白对照组外,其余各组用kligman法建立兔耳痤疮模型,于造模成功后,予模型组、夫西地酸乳膏组、苦参颗粒100、200、400mg/ml组分别涂敷生理盐水和相应药物,每日一次,连续14d。通过HE染色显微镜下判断其治疗效果;免疫组化检测TNF-α、IL-6、IL-8蛋白的表达;Western blot法检测p-p38MAPK、p-ERK、p38MAPK、ERK蛋白表达;ELISA测定法p-p38MAPK、p-ERK蛋白的含量。结果:与空白组比较,模型组TNF-α、IL-6、IL-8 MOD值和p-p38MAPK、p-ERK表达明显升高,p38MAPK、ERK表达明显下降;与模型组相比,给药各组TNF-α、IL-6和IL-8 MOD值和p-p38MAPK、p-ERK表达明显降低,p38MAPK、ERK表达明显增加。结论:苦参颗粒溶液能降低TNF-α、IL-6、IL-8含量,下调p-p38MAPK、p-ERK蛋白表达,上调p38MAPK、ERK蛋白表达,干预ERK、p38MAPK通路,从而干预痤疮的形成,对痤疮有疗效。
Objective:To investigate the effect of Kushen granule solution on p38 MAPK/ERK related signaling pathway in rabbit ear acne model and its therapeutic effect on acne.Methods:Kligman method was used to established rabbit ear acne model, except for the blank control group. After modeling, drugs or saline were daily given to rats in corresponding groups: the model group,the positive control group,and three doses of Kushen granule solution groups(100、200、400 mg/ml), for 14 days constantly. The therapeutic effect was observed by HE staining microscope. The expressions of TNF-α,IL-6 and IL-8 protein was detected by IHC method(immunohistochemistry). Protein expression of p-p38 MAPK,p-ERK,p38 MAPK and ERK was determined by Western blot. Protein expression of p-p38 MAPK and p-ERK was detected by ELISA.Results:Compared with the blank control group, levels of TNF-α,IL-6 and IL-8 in the model control group were increased,the protein expression of p-p38 MAPK and p-ERK was significantly increased, the protein expression of p38 MAPK and ERK was significantly decreased. Compared with the model group,levels of TNF-α,IL-6 and IL-8 protein in all Kushen granule groups were significantly decreased, the protein expression of p-p38 MAPK and p-ERK protein was significantly decreased,the protein expression of p38 MAPK and ERK protein was significantly increased.Conclusion:Kushen granule solution can decrease the expression levels of TNF-α、IL-6、IL-8、p-p38 MAPK and p-ERK,increase the levels of p38 MAPK and ERK,and intervene in the p38 MAPK/ERK signal pathway. It has certain effect on acne by interfering the formation of acne.
Objective:To investigate the effect of Kushen granule solution on p38 MAPK/ERK related signaling pathway in rabbit ear acne model and its therapeutic effect on acne.Methods:Kligman method was used to established rabbit ear acne model, except for the blank control group. After modeling, drugs or saline were daily given to rats in corresponding groups: the model group,the positive control group,and three doses of Kushen granule solution groups(100、200、400 mg/ml), for 14 days constantly. The therapeutic effect was observed by HE staining microscope. The expressions of TNF-α,IL-6 and IL-8 protein was detected by IHC method(immunohistochemistry). Protein expression of p-p38 MAPK,p-ERK,p38 MAPK and ERK was determined by Western blot. Protein expression of p-p38 MAPK and p-ERK was detected by ELISA.Results:Compared with the blank control group, levels of TNF-α,IL-6 and IL-8 in the model control group were increased,the protein expression of p-p38 MAPK and p-ERK was significantly increased, the protein expression of p38 MAPK and ERK was significantly decreased. Compared with the model group,levels of TNF-α,IL-6 and IL-8 protein in all Kushen granule groups were significantly decreased, the protein expression of p-p38 MAPK and p-ERK protein was significantly decreased,the protein expression of p38 MAPK and ERK protein was significantly increased.Conclusion:Kushen granule solution can decrease the expression levels of TNF-α、IL-6、IL-8、p-p38 MAPK and p-ERK,increase the levels of p38 MAPK and ERK,and intervene in the p38 MAPK/ERK signal pathway. It has certain effect on acne by interfering the formation of acne.
引文
[1]Zaenglein A L,Pathy A L,Schlosser B J,et al.Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol,2016,(74)∶945～973.
[2]Wolk K,Warszawska K,Hoeflich C,et al.Deficiency of IL-22 contributes to a chronic inflammatorydisease.pathogenetic mechanisms in acne inversa,2011,186∶1228～1239.
[3]古建梅,姜醒,李明杰.黄连牡蛎膏对兔耳痤疮模型抗角化作用的研究.中国现代医药杂志,2008,10(4)∶33～34.
[4]顾炜,张小卿,吴景东.痤疮合剂对兔耳痤疮模型MAPK相关信号通路影响.辽宁中医药大学学报,2017,(8)∶12～17.
[5]项蕾红.中国痤疮治疗指南(2014修订版).临床皮肤科杂志.2015,44(1)∶52～57.
[6]纪薇,沈德凯,唐洁.艾叶挥发油对兔耳痤疮模型的作用及其机制的实验研究.云南中医学院学报,2017,40(1)∶18～21.
[7]王海琦,崔鸿峥,李畅.月见草油调节p38MAPK、NF-κB信号通路抗炎治疗痤疮的实验.中药药理与临床,2018,34(2)∶62～67.
[8]韩琳,王洪新,鲁美丽.黄芪多糖通过抑制NF-κB和JNK信号通路减轻LPS诱导的小鼠心肌细胞凋亡.中国药理学通报,2018,34(2)∶243～249.
[9]郭丽红,吴景东.雄激素对痤疮影响及治疗.辽宁中医药大学学报,2009,11(1)∶70～71.
[10]Tomida S,Nguyen L,Chiu B H,et al.Pan-genome and comparative genome analyses of Propionibacteriumacnes reveal its genomic diversity in the healthy and diseased human skinmicrobiome.Mbio,2013,(4)∶3～13.
[11]Stanczyk E,Carmina FI,Godwin AJ,et al.The association of serum and rosterone glucuronide with inflarurrmtory lesions in worflen with adult acne.J Endocrinol Invest,2009,36(8)∶865.
[12]王海琦,崔鸿峥,李畅.月见草油调节p38MAPK、NF-κB信号通路抗炎治疗痤疮的实验.中药药理与临床,2018,34(2)∶62～67.
[13]高尚璞,杨芮姗,李咏梅,等.养阴清肺方治疗女性青春期后痤疮33例临床观察.中医杂志,2013,54(2)∶134～137.
[14]杨智,邹勇莉,顾华,等.环境及遗传因素对痤疮发病影响的研究.皮肤病与性病,2009,31(3)∶5～10.
[15]刘越阳,李铁男,王强,等.复方甘草酸苷联合丹参酮ⅡA治疗继发于皮炎湿疹的红皮病疗效观察.中华皮肤科杂志,2011,44(6)∶443.
[16]Wang X,Tournier C.Regulation of cellular functions by the ERK5 signaling pathway.Cell Signal,2006,18(6)∶753～760.
[17]Yang F,Yin Y,Wang F,et al.mi R-17-5p Promotes migration of human hepatocellular carcinoma cells thtough the p38 mitogen-activated protein kinase-heat shock protein 27 pathway.Hepatology,2010,51(5)∶1614～1623.
[18]Ana Cuenda,Simon Rousseau.p38 MAP-Kinases pathway regulation,function and role in human diseases.Biochimical Biophysical Acta,2007,1773(8)∶1358～1375.
[19]孔学礼,王亚楠,丛心宇,等.咯利普兰通过MAPK/ERK信号通路抑制中性粒细胞的黏附.北京农学院学报,2018,33(2)∶2～7.
[20]国家药典委员会.中华人民共和国药典:1 部.北京.中国医药科技出版社,2010∶188.
[21]Zhang B,Liu Z Y,Li Y Y.Antiinflammatory effects ofmatrine in LPS-induced acute lung injury in mice.European Journal Of Pharmaceutical Sciences,2011,44(5)∶573～579.
[22]Chang C,Liu S P,Fang C H.Effects of matrine on theproliferation of HT29 human colon cancer cells and its anti-tumor mechanism.Oncology Letters,2013,6(3)∶699～704.
[23]Zhang X C,Jin L L,Cui Z.Antiparasitic effects ofoxymatrine and matrine against Toxoplasma gondii in vitroand in vivo.Experimental Parasitology,2016,165∶95～102.
[24]Xu W H,Hu H G,Tian Y.Bioactive Compound Revealsa Novel Function for Ribosomal Protein S5 in Hepatic Stel-late Cell Activation and Hepatic Fibrosis.Hepatolo-gy,2014,60 ( 2)∶648～660.
[2]Wolk K,Warszawska K,Hoeflich C,et al.Deficiency of IL-22 contributes to a chronic inflammatorydisease.pathogenetic mechanisms in acne inversa,2011,186∶1228～1239.
[3]古建梅,姜醒,李明杰.黄连牡蛎膏对兔耳痤疮模型抗角化作用的研究.中国现代医药杂志,2008,10(4)∶33～34.
[4]顾炜,张小卿,吴景东.痤疮合剂对兔耳痤疮模型MAPK相关信号通路影响.辽宁中医药大学学报,2017,(8)∶12～17.
[5]项蕾红.中国痤疮治疗指南(2014修订版).临床皮肤科杂志.2015,44(1)∶52～57.
[6]纪薇,沈德凯,唐洁.艾叶挥发油对兔耳痤疮模型的作用及其机制的实验研究.云南中医学院学报,2017,40(1)∶18～21.
[7]王海琦,崔鸿峥,李畅.月见草油调节p38MAPK、NF-κB信号通路抗炎治疗痤疮的实验.中药药理与临床,2018,34(2)∶62～67.
[8]韩琳,王洪新,鲁美丽.黄芪多糖通过抑制NF-κB和JNK信号通路减轻LPS诱导的小鼠心肌细胞凋亡.中国药理学通报,2018,34(2)∶243～249.
[9]郭丽红,吴景东.雄激素对痤疮影响及治疗.辽宁中医药大学学报,2009,11(1)∶70～71.
[10]Tomida S,Nguyen L,Chiu B H,et al.Pan-genome and comparative genome analyses of Propionibacteriumacnes reveal its genomic diversity in the healthy and diseased human skinmicrobiome.Mbio,2013,(4)∶3～13.
[11]Stanczyk E,Carmina FI,Godwin AJ,et al.The association of serum and rosterone glucuronide with inflarurrmtory lesions in worflen with adult acne.J Endocrinol Invest,2009,36(8)∶865.
[12]王海琦,崔鸿峥,李畅.月见草油调节p38MAPK、NF-κB信号通路抗炎治疗痤疮的实验.中药药理与临床,2018,34(2)∶62～67.
[13]高尚璞,杨芮姗,李咏梅,等.养阴清肺方治疗女性青春期后痤疮33例临床观察.中医杂志,2013,54(2)∶134～137.
[14]杨智,邹勇莉,顾华,等.环境及遗传因素对痤疮发病影响的研究.皮肤病与性病,2009,31(3)∶5～10.
[15]刘越阳,李铁男,王强,等.复方甘草酸苷联合丹参酮ⅡA治疗继发于皮炎湿疹的红皮病疗效观察.中华皮肤科杂志,2011,44(6)∶443.
[16]Wang X,Tournier C.Regulation of cellular functions by the ERK5 signaling pathway.Cell Signal,2006,18(6)∶753～760.
[17]Yang F,Yin Y,Wang F,et al.mi R-17-5p Promotes migration of human hepatocellular carcinoma cells thtough the p38 mitogen-activated protein kinase-heat shock protein 27 pathway.Hepatology,2010,51(5)∶1614～1623.
[18]Ana Cuenda,Simon Rousseau.p38 MAP-Kinases pathway regulation,function and role in human diseases.Biochimical Biophysical Acta,2007,1773(8)∶1358～1375.
[19]孔学礼,王亚楠,丛心宇,等.咯利普兰通过MAPK/ERK信号通路抑制中性粒细胞的黏附.北京农学院学报,2018,33(2)∶2～7.
[20]国家药典委员会.中华人民共和国药典:1 部.北京.中国医药科技出版社,2010∶188.
[21]Zhang B,Liu Z Y,Li Y Y.Antiinflammatory effects ofmatrine in LPS-induced acute lung injury in mice.European Journal Of Pharmaceutical Sciences,2011,44(5)∶573～579.
[22]Chang C,Liu S P,Fang C H.Effects of matrine on theproliferation of HT29 human colon cancer cells and its anti-tumor mechanism.Oncology Letters,2013,6(3)∶699～704.
[23]Zhang X C,Jin L L,Cui Z.Antiparasitic effects ofoxymatrine and matrine against Toxoplasma gondii in vitroand in vivo.Experimental Parasitology,2016,165∶95～102.
[24]Xu W H,Hu H G,Tian Y.Bioactive Compound Revealsa Novel Function for Ribosomal Protein S5 in Hepatic Stel-late Cell Activation and Hepatic Fibrosis.Hepatolo-gy,2014,60 ( 2)∶648～660.