摘要
目的:探究积雪草总苷对老年消化不良(FD)模型大鼠胃肠动力及肠神经系统(ENS)保护作用的量效关系及机制。方法:将16月龄老年雄性SD大鼠随机分为空白对照组、模型组和积雪草总苷低、中、高剂量组(15、30、60 mg/kg),每组8只。采用夹尾刺激联合不规则饮食法持续4周以建立老年大鼠FD模型。造模完成后隔日,给药组大鼠灌胃相应剂量积雪草总苷药液,对照组和模型组大鼠灌胃等容生理盐水,每日1次,连续15 d。采用酶联免疫吸附测定法检测大鼠血清中胃动素(MTL)、血管活性肠肽(VIP)的含量;测定大鼠胃排空率和小肠推进比;采用免疫荧光法和免疫组织化学法检测大鼠胃窦组织中ENS标志物[中枢神经特异性蛋白(S100β)和胶质细胞源性神经营养因子(GDNF)]的表达情况;采用Western blotting法检测胃窦组织中S100β、胶质细胞原纤维酸性蛋白(GFAP)、蛋白基因产物9.5(PGP9.5)、GDNF、磷酸化丝裂原活化蛋白激酶激酶(p-MEK)以及磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白的表达水平。结果:与空白对照组比较,模型组和积雪草总苷低、中剂量组大鼠胃排空率和小肠推进比以及血清中MTL含量和胃窦组织中PGP9.5蛋白表达水平显著降低,血清中VIP含量和胃窦组织中S100β、GFAP、GDNF、pMEK、p-ERK1/2蛋白表达水平均显著升高(P<0.05)。与模型组比较,积雪草总苷各剂量组大鼠胃排空率和小肠推进比均显著升高(P<0.05);除积雪草总苷低剂量组GFAP蛋白表达水平变化不显著(P>0.05)外,各剂量组大鼠血清中MTL含量和胃窦组织中PGP9.5蛋白表达水平均显著升高,血清中VIP含量和胃窦组织中S100β、GFAP、GDNF、p-MEK、p-ERK1/2蛋白表达水平均显著降低(P<0.05)。上述胃肠动力指标含量和相关因子蛋白表达水平有部分或大多数在积雪草总苷不同剂量组之间有显著差异(P<0.05),且高剂量组各指标可恢复至与空白对照组无显著差异�
OBJECTIVE:To explore the dose-effect relationship and mechanism of protective effects of total asiaticoside(TA)on gastrointestinal motility and enteric nervous system(ENS) in aged functional dyspepsia(FD) model rats. METHODS:Aged male SD rats of 16 months old were randomly divided into blank control group,model group,TA low dose,medium dose and high dose groups(15,30,60 mg/kg),with 8 rats in each group. FD model was established by tail-stimulation combined with irregular diet for 4 weeks. The next day after modeling,administration groups were given relevant doses of TA solution intragastrically;control group and model group were given constant volume of normal saline intragastrically,once a day,for consecutive 15 d.Gastric emptying rate and small intestinal propulsion rate of rats were examined. ELISA were used to detect serum contents of MTL and VIP. Immunofluorescence and immunohistochemistry were proposed to measure the expression of ENS marker(S100β and GDNF) in gastric antrum tissue. The protein expression of S100β,GFAP,PGP9.5,GDNF,p-MEK and p-ERK1/2 in gastric antrum tissue were measured by Western blotting assay. RESULTS:Compared with blank control group,gastric emptying rate and small intestinal propulsion rate,serum MTL content and protein expression of PGP9.5 in gastric antrum tissue of model and TA low,medium dose group were decreased significantly,while serum VIP content,protein expressions of S100β,GFAP,GDNF,pMEK and p-ERK1/2 in gastric tissue were increased significantly(P<0.05). Compared with model group,gastric emptying rate and small intestinal propulsion rate of TA groups were increased significantly(P<0.05);except for GFAP protein in TA low dose group(P>0.05),the serum MTL content and the expression of PGP9.5 protein in gastric antrum tissue of rats in TA groups were increased significantly,while serum VIP content,protein expression of S100β,GFAP,GDNF,p-MEK and p-ERK1/2 in gastric antrum tissue were decreased significantly(P<0.05). Some or most of the content of gastrointestinal motility in
作者
田徐露
蓝程
岑运光
王太昊
崔晓燕
TIAN Xulu;LAN Cheng;CEN Yunguang;WANG Taihao;CUI Xiaoyan(Health Care Center,Hainan Provincial People’s Hospital,Haikou 570311,China;Dept.of Gastroenterology,Hainan Provincial People’s Hospital,Haikou 570311,China)
出处
《中国药房》
CAS
北大核心
2020年第12期1429-1435,共7页
China Pharmacy
基金
国家自然科学基金资助项目(No.81860102)。
