茯苓酸调节cAMP/PKA/CREB信号通路对脑出血大鼠脑组织损伤的影响  

Effect of pachymenic acid on brain tissue damage in rats with cerebral hemorrhage by regulating the cAMP/PKA/CREB signaling pathway

作　　者：许永杰 贾晓龙 王燕领 XU Yongjie;JIA Xiaolong;WANG Yanling(CT Room,Handan First Hospital,Handan,Hebei 056002,China)

机构地区：[1]邯郸市第一医院CT室,河北邯郸056002

出　　处：《安徽医药》2025年第5期898-902,I0001,共6页Anhui Medical and Pharmaceutical Journal

基　　金：河北省卫生健康委基金项目(20210215)。

摘　　要：目的探究茯苓酸对脑出血大鼠脑组织损伤的影响及其可能作用机制。方法2023年1―5月将大鼠按随机数字表法分为假手术组、模型组、茯苓酸低、高剂量组和茯苓酸高剂量+H-89(cAMP抑制剂)组,每组10只。采用Zea-Longa评分法评估各组大鼠神经功能;酶联免疫吸附法检测血清白细胞介素1β(IL-1β)、白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)、环磷酸腺苷(cAMP)水平;苏木精-伊红(HE)染色观察海马神经元损伤;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色检测海马神经元凋亡;检测B细胞淋巴瘤(Bcl-2)、Bcl-2相关X蛋白(Bax)、cAMP/蛋白激酶A(PKA)/环磷酸腺苷反应元件结合蛋白(CREB)通路蛋白表达。结果与假手术组相比,模型组大鼠海马神经元结构严重损伤,神经功能评分(2.80±0.37)分比(0.10±0.02)分、IL-1β(342.58±29.73)ng/L比(30.67±2.84)ng/L、TNF-α(253.70±23.49)ng/L比(14.38±1.26)ng/L水平、神经元凋亡率(26.58±2.26)%比(3.37±0.42)%、Bax蛋白表达(0.91±0.08比0.36±0.03)升高,IL-10(42.76±4.04)ng/L比(178.93±16.63)ng/L、cAMP(1.42±0.13)μg/L比(2.86±0.27)μg/L水平、Bcl-2(0.28±0.02比0.78±0.06)、p-PKA/PKA(0.51±0.04比1.16±0.11)、CREB/p-CREB(0.32±0.03比0.87±0.07)蛋白表达水平降低(P<0.05);与模型组相比,茯苓酸低、高剂量组大鼠海马神经元损伤减轻,神经功能评分、IL-1β、TNF-α水平、神经元凋亡率、Bax蛋白表达降低,IL-10、cAMP水平、Bcl-2、p-PKA/PKA、CREB/p-CREB蛋白表达水平升高(P<0.05);cAMP抑制剂H-89可部分逆转茯苓酸对脑出血大鼠的改善作用(P<0.05)。结论茯苓酸可减轻脑出血大鼠脑组织损伤和炎症反应,可能与激活cAMP/PKA/CREB信号通路有关。Objective To investigate the effect of pachymaric acid on brain tissue injury in rats with cerebral hemorrhage and its possible mechanism.Methods From January to May 2023,SD rats were separated into sham surgery group,model group,low-dose pachymenate group,high-dose pachymenate group,and high-dose pachymenate+H-89(cAMP inhibitor)group according to random number table method.The neurological function of rats in each group was evaluated by Zea Longa scoring;enzyme linked immunosorbent assay(ELISA)was applied to detect serum levels of interleukin-1β(IL-1β),interleukin-10(IL-10),tumor necrosis factorα(TNF-α),and cyclic adenosine phosphate(cAMP);hematoxylin-eosin(HE)staining was applied to observe hippocampal neuronal damage;deoxyribonucleotide end transferase mediated notch end labeling(TUNEL)staining was applied to detect hippocampal neuronal apoptosis;the expression of B-cell lymphoma(Bcl-2),Bcl-2 associated X protein(Bax),cAMP/protein kinase A(PKA)/cyclic adenosine phosphate reaction element binding protein(CREB)pathway protein was detected.Results Compared with the sham surgery group,the hippocampal neuronal structure of rats in the model group was severely damaged,the neurological function score(2.80±0.37)points vs.(0.10±0.02)points,levels of IL-1β(342.58±29.73)ng/L vs.(30.67±2.84)ng/L and TNF-α(253.70±23.49)ng/L vs.(14.38±1.26)ng/L,neuronal apoptosis rate(26.58±2.26)%vs.(3.37±0.42)%,and the protein expression of Bax(0.91±0.08 vs.0.36±0.03)were obviously increased,the levels of IL-10(42.76±4.04)ng/L vs.(178.93±16.63)ng/L and cAMP(1.42±0.13)μg/L vs.(2.86±0.27)μg/L,the protein expression of Bcl-2(0.28±0.02 vs.0.78±0.06),p-PKA/PKA(0.51±0.04 vs.1.16±0.11),and CREB/p-CREB(0.32±0.03 vs.0.87±0.07)were obviously reduced(P<0.05);compared with the model group,the structural damage of hippocampal neurons in the low and high dose Poric acid groups was obviously reduced,the neurological function score,levels of IL-1βand TNF-α,neuronal apoptosis rate,and the protein expression of Bax were obvious

关 键 词：茯苓属 cAMP/PKA/CREB信号通路 脑出血 

分 类 号：R285.5[医药卫生—中药学]