首页|普萘洛尔通过负调控VEGF和PI3K/Akt信号通路抑制大鼠烧伤后的瘢痕形成

普萘洛尔通过负调控VEGF和PI3K/Akt信号通路抑制大鼠烧伤后的瘢痕形成

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目的 探讨普萘洛尔对大鼠烧伤后瘢痕形成的影响及机制.方法 将30只SD大鼠随机分为对照组、模型组、普萘洛尔低剂量组、普萘洛尔中剂量组、普萘洛尔高剂量组,每组各6只.对照组大鼠正常饲养;恒温恒压烫伤仪烫伤其它各组大鼠背部皮肤构建模型组.普萘洛尔低剂量组、普萘洛尔中剂量组、普萘洛尔高剂量组大鼠分别使用剂量为12.5 mg/kg、25 mg/kg、50 mg/kg的普萘洛尔进行灌胃处理,持续灌胃3周.每周观察记录大鼠状态和瘢痕状况.利用免疫荧光法检测各组瘢痕细胞中血管标志物CD31和CD34的表达.采用实时荧光逆转录聚合酶链反应(reverse transcription quantitative polymerase chain reaction,RT-qPCR)检测各组大鼠癒痕组织内血管内皮生长因子(vascular en-dothelial growth factor,VEGF)、磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)和蛋白激酶 B(protein kinase B,Akt)的mRNA表达;采用免疫组织化学法检测VEGF、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-Akt)、磷酸化磷脂酰肌醇-3激酶(phosphorylated phosphatidylinositol 3-kinase,p-PI3K)的蛋白表达情况.结果 经过治疗后,与模型组比较,普萘洛尔低、中、高剂量组的瘢痕组织厚度、血管分布、柔软性评分均明显降低(P均<0.05).与模型组比较,普萘洛尔低、中、高剂量组大鼠瘢痕组织内CD31和CD34表达显著降低(P均<0.05).与对照组比较,模型组和普萘洛尔低、中、高剂量组大鼠瘢痕组织内VEGF、PI3K和Akt的mRNA表达,p-PI3K、p-Akt和VEGF的蛋白表达显著增加(P均<0.01);与模型组比较,普萘洛尔低、中、高剂量组大鼠瘢痕组织内VEGF、PI3K和Akt的mRNA表达,p-PI3K、p-Akt和VEGF的蛋白表达显著下调(P均<0.05);与普萘洛尔低剂量组相比,普萘洛尔中剂量组和普萘洛尔高剂量组大鼠瘢痕组织内VEGF、PI3K和Akt的mRNA表达,p-PI3K、p-Akt和VEGF蛋白表达显著下调(P均<0.05);与普萘洛尔中剂量组相比,普萘洛尔高剂量组大鼠瘢痕组织内VEGF、PI3K和Akt的mRNA表达,p-PI3K、p-Akt和VEGF蛋白表达显著下调(P均<0.05).结论 普萘洛尔通过负调控VEGF和PI3K/Akt信号通路抑制血管生成,从而有效治疗瘢痕.
Inhibition of Propranolol on Burn-induced Scar in Rats by Negatively-regulating VEGF and PI3K/Akt Signal Pathway
Objective To investigate the effects of propranolol on burn-induced scar in rats and its mechanism.Methods A total of 30 SD rats were randomly divided into control group,model group,low,medium and high-dose pro-pranolol groups,with 6 rats in each.The control group was raised normally;the model groups were constructed by scal-ding the back skin of rats in other groups by scald apparatus with constant temperature and isopiestic pressure.The low-dose,medium-dose and high-dose propranolol groups were treated with 12.5 mg/kg,25 mg/kg and 50 mg/kg propranolol by gavage for 3 weeks respectively.The state and scar status of the rats were observed and recorded every week.The ex-pression of vascular markers CD31 and CD34 in scar cells of each group were detected by immunofluorescence.The mR-NA expressions of vascular endothelial growth factor(VEGF),phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)of scar tissues in each group of rats were detected by reverse transcription quantitative polymerase chain reaction(RT-qPCR);the expressions of VEGF,phos-phorylated protein kinase B(p-Akt)and phosphorylated phosphatidylinositol 3-kinase(p-PI3K)were detected by immunohistochemical method.Results After the treat-ments,compared with the model group,the thickness,vascular distribution and pliability scores of scar tissues in low-dose,medium-dose and high-dose propranolol groups significantly decreased(all P<0.05).Compared with the model group,the expressions of CD31 and CD34 in scar tissues decreased in low-dose,medium-dose and high-dose propranolol groups(all P<0.05).Compared with control group,and the mRNA expressions of VEGF,PI3K and Akt,and the pro-tein expressions of p-PI3K,p-Akt and VEGF in scar tissues of rats in model group and low-dose,medium-dose and high-dose propranolol groups significantly increased(all P<0.01);compared with the model group,the mRNA expressions of VEGF,PI3K and Akt,and the protein expressions of p-PI3K,p-Akt and VEGF in scar tissues of rats in low-dose,medi-um-dose and high-dose propranolol groups were significantly down-regulated(all P<0.05);compared with the low-dose propranolol group,the mRNA expressions of VEGF,PI3K and Akt,and the protein expressions of p-PI3K,p-Akt and VEGF in scar tissues of rats in medium-dose and high-dose propranolol groups were significantly down-regulated(all P<0.05);compared with the medium-dose propranolol group,the mRNA expressions of VEGF,PI3K and Akt,and the protein expressions of p-PI3K,p-Akt and VEGF in scar tissues of rats in high-dose propranolol group were significantly down-regulated(all P<0.05).Conclusion Propranolol inhibits angiogenesis by negatively regulating VEGF and PI3K/Akt signaling pathways,which can effectively treating scars.

ScarPropranololPhosphatidylinositol 3-kinase/protein kinase B signaling pathwayAngiogenesis

丁子明、徐凯

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430081 湖北武汉,武汉科技大学医学部医学院

中部战区总医院烧伤整形科

瘢痕 普萘洛尔 磷脂酰肌醇-3激酶/蛋白激酶B信号通路 血管生成

湖北省卫生计生委联合基金

WJ2018H0084

2024

华南国防医学杂志
广州军区医学科学技术委员会

华南国防医学杂志

CSTPCD
影响因子:0.748
ISSN:1009-2595
年,卷(期):2024.38(3)
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