五倍子瘢痕膏对瘢痕疙瘩mTOR信号通路的调控作用研究
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摘要
目的:观察五倍子瘢痕膏对瘢痕疙瘩哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路关键分子磷脂酰肌醇3-激酶(Phosphatidylionsitol 3-kinase,PI3K)、10号染色体张力缺失蛋白磷酸酶(Phosphatase and tensin homolog deleted on chromosome ten,PTEN)、蛋白激酶B (Protein Kinase B,Akt)、mTOR表达的影响。方法:将36只裸鼠瘢痕疙瘩模型随机分成治疗组和模型组,每组18只。治疗组涂抹五倍子瘢痕膏,模型组仅涂抹制作五倍子瘢痕膏的基质,每天3次,连续30天。然后应用免疫组化检测治疗组和模型组瘢痕疙瘩及正常皮肤组织中PI3K、PTEN、Akt、mTOR的表达。结果:与正常皮肤组比较,模型组PI3K、Akt、mTOR表达阳性率升高,而PTEN表达阳性率降低,差异均有统计学意义(P <0.05);与模型组比较,治疗组PI3K、Akt、mTOR表达阳性率降低,而PTEN表达阳性率升高,差异均有统计学意义(P <0.05)。应用Person法对瘢痕疙瘩中mTOR信号通路各关键信号分子表达相关性进行分析,结果 PTEN与PI3K、mTOR、Akt呈负相关,PI3K与mTOR、Akt呈正相关,Akt与mTOR呈正相关。结论:五倍子瘢痕膏抑制瘢痕疙瘩成纤维细胞增殖的机制与其上调mTOR信号通路中PTEN表达及下调PI3K、Akt、mTOR表达有关。
Objective: To observe the effect of Wubeizi Banhen ointment on expressions of such key molecules as phosphatidylionsitol 3-kinase(PI3 K),phosphatase and tensin homolog deleted on chromosome ten(PTEN) and protein Kinase B(Akt) and m TOR in the mammalian target of rapamycin(mTOR) signaling pathway of keloid in mammals. Methods:Divided the models of 36 nude mice with keloid into the treatment group and the model group randomly,18 mice in each group. The treatment group received the external application of Wubeizi Banhen ointment, while the model group only received the external application of the base for making Wubeizi Banhen ointment, three times per day and for 30 days continuously.Detected the expressions of PTEN,PI3 K,Akt and m TOR in keloid and normal skin of the treatment group and the model group via immunohistochemical detection. Results:Comparing with the normal skin group,the positive rate of expressions of PI3 K, Akt and m TOR in the model group was increased respectively, and the positive rate of expressions of PTEN was decreased,differences being significant(P < 0.05);comparing with the model group,the positive rate of expressions of PI3 K,Akt and m TOR in the treatment group was decreased respectively, and the positive rate of expressions of PTEN was increased, differences being significant(P < 0.05). A correlation analysis was conducted for the expressions of each key molecule in the m TOR signaling pathway of keloid via Person method. As the results showed, PTEN had a negative correlation with PI3 K,mTOR and Akt,PI3 K had a positive correlation with m TOR and Akt,and Akt had a positive correlation with m TOR. Conclusion:The mechanism of Wubeizi Banhen ointment suppressing fibroblast proliferation of keloid is related to its up-regulation of expression of PTEN and its down-regulation of expressions of PI3 K, Akt and m TOR in the m TOR signaling pathway.
Objective: To observe the effect of Wubeizi Banhen ointment on expressions of such key molecules as phosphatidylionsitol 3-kinase(PI3 K),phosphatase and tensin homolog deleted on chromosome ten(PTEN) and protein Kinase B(Akt) and m TOR in the mammalian target of rapamycin(mTOR) signaling pathway of keloid in mammals. Methods:Divided the models of 36 nude mice with keloid into the treatment group and the model group randomly,18 mice in each group. The treatment group received the external application of Wubeizi Banhen ointment, while the model group only received the external application of the base for making Wubeizi Banhen ointment, three times per day and for 30 days continuously.Detected the expressions of PTEN,PI3 K,Akt and m TOR in keloid and normal skin of the treatment group and the model group via immunohistochemical detection. Results:Comparing with the normal skin group,the positive rate of expressions of PI3 K, Akt and m TOR in the model group was increased respectively, and the positive rate of expressions of PTEN was decreased,differences being significant(P < 0.05);comparing with the model group,the positive rate of expressions of PI3 K,Akt and m TOR in the treatment group was decreased respectively, and the positive rate of expressions of PTEN was increased, differences being significant(P < 0.05). A correlation analysis was conducted for the expressions of each key molecule in the m TOR signaling pathway of keloid via Person method. As the results showed, PTEN had a negative correlation with PI3 K,mTOR and Akt,PI3 K had a positive correlation with m TOR and Akt,and Akt had a positive correlation with m TOR. Conclusion:The mechanism of Wubeizi Banhen ointment suppressing fibroblast proliferation of keloid is related to its up-regulation of expression of PTEN and its down-regulation of expressions of PI3 K, Akt and m TOR in the m TOR signaling pathway.
引文
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[2]丁继存,严月华,翟晓翔,等.五倍子瘢痕膏治疗瘢痕疙瘩的疗效观察[J].河北医科大学学报,2007,28(5):356-359.
[3]Ji CD,Zhi MT,Xiao XZ,et al.The effects of Wubeizi Ointment on the proliferation of Keloid-Derived Fibroblasts[J].Cell Biochem Biophys,2015,71(1):431-435.
[4]Kischer CW,Pindur J,Shetlar MR,et al.Implants of hypertrophic scars and keloids into the nude(athymic)mouse:viability and morphology[J].Trauma,1989,29:672-677.
[5]Shimizu M,Saitoh Y,Itoh H.Immunohistochemical staining of Ha-ras oncogene product in normal,benign,and malignant human pancreatic tissue[J].Human Pathol,1990,21(6):607.
[6]赵炳南,张志礼.简明中医皮肤病学[M].北京:中国中医药出版社,2014:248-249.
[7]翟晓翔,丁继存,陈向辉.五倍子瘢痕膏水溶液对瘢痕疙瘩成纤维细胞Ⅰ、Ⅲ前胶原基因表达的影响[J].福建中医药,2010,41(4):53-55.
[8]Steelman LS,Chappell WH,Abrams SL,et a1.Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/m TOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging[J].Aging(Albany NY),2011,3(3):192-222.
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