基于MAPK、PI3K/AKT信号通路探讨散血明目片防治增殖性玻璃体视网膜病变机制  

Mechanism of Sanxue Mingmu Tablet in preventing and treating proliferative vitreoretinopathy based on MAPK and PI3K/AKT signal pathways

作　　者：刘晓清 谭涵宇[1] 彭俊[2] 秦惠钰 田野 彭清华[1] 吴权龙[2] LIU Xiao-qing;TAN Han-yu;PENG Jun;QIN Hui-yu;TIAN Ye;PENG Qing-hua;WU Quan-long(Hunan University of Chinese Medicine,Changsha 410208,China;First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学第一附属医院,长沙410007

出　　处：《中华中医药杂志》2020年第5期2355-2361,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中医药防治五官科疾病湖南省重点实验室建设项目(No.2017TP1018);湖南省中医药防治耳鼻喉疾病与视功能保护工程研究中心开放基金项目(No.2018YGCO4);湖南省中医药管理局科研项目(No.201622);湖南省研究生科研创新项目(No.CX2018B499,No.CX2018B490);国家中医药管理局中医眼科学重点学科建设项目(No.国家中医药[2009]30号)

摘　　要：目的:通过建立兔外伤性增殖性玻璃体视网膜病变(PVR)模型,观察散血明目片对其视网膜增殖膜中磷脂酰肌醇-3(PI3K)、蛋白激酶B(AKT)、丝裂原活化蛋白激酶(MEK)、丝裂原活化细胞信号调节激酶(P38MAPK)蛋白的表达影响。方法:将42只新西兰大白兔随机分为空白(A)组、模型(B)组、散血明目片(C)组、PD98059干预(D)组、LY294002干预(E)组、MK-2206干预(F)组、混合抑制剂干预(G)组,每组6只。造模后30min,向D、E、F、G组玻璃体腔内分别注射0.1mL PD98059、LY294002、MK-2206及3种混合抑制剂。B、C组则予以玻璃体腔内注射0.1mL 0.9%氯化钠溶液。术后第1天,C组予以散血明目片10mg/kg溶液灌胃,除A组其余组以0.9%氯化钠溶液10mL/kg灌胃,连续28d。造模后观察眼底情况,取材后光镜下观察视网膜各层的形态结构,Western Blot法检测各组视网膜增殖膜PI3K、AKT、MEK、P38MAPK蛋白的表达情况。结果:散血明目片能够抑制炎性细胞的增殖及浸润,减少增生。与A组比较,B、C、D、E、F组PI3K蛋白表达均显著升高(P<0.01,P<0.05);与B组比较,各给药组PI3K蛋白表达显著降低(P<0.01);与C组比较,D、E、F组PI3K蛋白表达显著升高(P<0.01)。与A组比较,B、D、E、F组AKT蛋白表达均显著升高(P<0.01);与B组比较,各给药组AKT蛋白表达均显著降低(P<0.01,P<0.05);与C组比较,D、E、F组AKT蛋白表达显著升高(P<0.01,P<0.05)。与A组比较,其余各组MEK蛋白表达均显著提高(P<0.01),与B组比较,各给药组MEK蛋白表达均显著降低(P<0.01,P<0.05);与C组比较,D、G组MEK蛋白表达显著降低(P<0.05),而E、F组MEK蛋白表达显著升高(P<0.01)。与A组比较,其余各组P38MAPK蛋白表达显著升高(P<0.01,P<0.05);与B组比较,各给药组P38MAPK蛋白表达均显著降低(P<0.01,P<0.05);与C组比较,D、E、F、G组P38MAPK蛋白表达均显著升高(P<0.01)。结论:散血明目片可以通过MAPK、PI3K/AKT信号通路降低PI3K、AKT、MEK、P38MAPK蛋白的表�Objective: To observe the effect of Sanxue Mingmu Tablet on the expression of PI3 K, AKT, MEK and P38 MAPK protein in the proliferative membrane of retina by establishing a rabbit model of traumatic proliferative vitreoretinopathy(PVR). Methods: Forty-two New Zealand white rabbits were randomly divided into blank group(A), model group(B), Sanxue Mingmu Tablet group(C), PD98059 group(D), LY294002 group(E), MK-2206 group(F) and inhibitor mixed group(G), each group 6 rabbits. After 30 minutes of modeling, 0.1 mL PD98059, LY294002, MK-2206 and three mixed inhibitors were injected into the vitreous cavity of group D, E, F and G, respectively. In group B and C, 0.1 mL 0.9% sodium chloride solution were injected into the vitreous cavity. On the first day after the operation, group C was given 10 mg/kg Sanxue Mingmu Tablet by gavage, except group A, the other groups were given 10 mL/kg 0.9% sodium chloride solution by gavage for 28 days. After the model was made, the fundus was observed, the morphological structure of each layer of retina was observed under the light microscope, and the expression of PI3 K, AKT, MEK and P38 MAPK protein in the proliferative membrane of retina were detected by Western Blot. Results: Sanxue Mingmu Tablet could inhibit the proliferation and infiltration of inflammatory cells and reduce the proliferation. Compared with group A, the expression of PI3 K protein in group B, C, D, E and F was significantly higher(P<0.01, P<0.05);compared with group B, the expression of PI3 K protein in group C, D, E, F and G was significantly lower(P<0.01);compared with group C, the expression of PI3 K protein in group D, E and F was significantly higher(P<0.01). Compared with group A, AKT protein expression in group B, D, E and F increased significantly(P<0.01);compared with group B, AKT protein expression in group C, D, E, F and G decreased significantly(P<0.01, P<0.05);compared with group C, AKT protein expression in group D, E and F increased significantly(P<0.01, P<0.05). Compared with group A, the expressi

关 键 词：增殖性玻璃体视网膜病变 散血明目片 磷脂酰肌醇-3 蛋白激酶B 丝裂原活化蛋白激酶 丝裂原活化细胞信号调节激酶 机制 

分 类 号：R285.5[医药卫生—中药学]