Page 35 - 《中国药房》2023年21期

·药学研究·

四磨汤口服液改善功能性消化不良模型大鼠的作用机制
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符 佳 ，周赛男（湖南中医药大学第一附属医院脾胃病科，长沙 410007）
中图分类号 R965；R285 文献标志码 A 文章编号 1001-0408（2023）21-2589-06
DOI 10.6039/j.issn.1001-0408.2023.21.04

摘 要 目的 探讨四磨汤口服液调控PTEN诱导假定激酶1（Pink1）/E3泛素连接酶（Parkin）轴对功能性消化不良（FD）模型大鼠
的改善作用及机制。方法 取SD雄性大鼠，利用不可预知的慢性应激法建立FD模型，然后随机分为模型组、阳性对照组（多潘立
酮片，3.5 mg/kg）、四磨汤组（四磨汤口服液，5.4 mL/kg），另设不造模的空白组，每组20只。各给药组大鼠灌胃相应药物，空白组和
模型组大鼠灌胃等体积生理盐水，每天1次，持续14 d。末次给药结束后，检测大鼠胃排空率和小肠推进率；检测大鼠血清中胃肠
激素[胃动素（MTL）、胃泌素（GAS）、胆囊收缩素（CCK）]含量；观察大鼠胃窦组织中卡哈尔间质细胞（ICC）线粒体结构；观察大鼠
胃窦组织中细胞色素C氧化酶Ⅳ（COX Ⅳ）和Parkin在线粒体中的共定位表达；检测大鼠胃窦组织中微管相关蛋白轻链3（LC3）、
p62、Pink1、Parkin蛋白的表达。结果 与空白组比较，模型组大鼠胃排空率、小肠推进率和血清中MTL、GAS含量以及p62蛋白表
达水平均显著降低（P＜0.05），血清中CCK含量和胃窦组织线粒体中COX Ⅳ、Parkin的共定位表达以及LC3、Pink1、Parkin蛋白表
达水平均显著升高（P＜0.05）；胃窦组织中ICC线粒体数量减少，线粒体空泡化，线粒体嵴模糊，自噬溶酶体较多。与模型组比较，
阳性对照组和四磨汤组大鼠上述指标水平均显著逆转（P＜0.05）；ICC 线粒体结构逐渐恢复，线粒体嵴清晰，自噬溶酶体减少。
结论 四磨汤口服液可改善FD模型大鼠的胃肠动力和胃肠激素水平，其作用机制可能与抑制Pink1/Parkin轴、阻断自噬有关。
关键词 四磨汤口服液；PTEN诱导假定激酶1；E3泛素连接酶；功能性消化不良；自噬

Mechanism of Simotang oral liquid in improving functional dyspepsia model rats
FU Jia，ZHOU Sainan（Dept. of Spleen and Stomach Disease， the First Affiliated Hospital of Hunan University
of Traditional Chinese Medicine， Changsha 410007， China）

ABSTRACT OBJECTIVE To explore the improvement effect and mechanism of Simotang oral liquid on functional dyspepsia
（FD） model rats by regulating PTEN-induced putative kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin） axis. METHODS SD male
rats were subjected to unpredictable chronic stress to establish an FD model， and were randomly grouped into the model group，
positive control group （Domperidone tablets， 3.5 mg/kg）， Simo decoction group （Simotang oral liquid， 5.4 mL/kg）， with 20 rats
in each group. The blank group without modeling was set up. Administration groups were given relevant medicine intragastrically，
blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 14 d. After
the last administration， the gastric emptying rate and small intestine propulsion rate of rats were detected. The contents of
gastrointestinal hormones [motilin （MTL）， gastrin （GAS） and cholecystokinin （CCK）] in rats were determined； the mitochondrial
structure of ICC in gastric antrum tissue of rats was observed； the immunofluorescence co-localization method was applied to
observe the expression of cytochrome C oxidase Ⅳ （COX Ⅳ） and Parkin in gastric antrum tissue of rats； the protein expressions
of LC3， p62， Pink1 and Parkin in gastric antrum tissue of rats were all detected. RESULTS Compared with the blank group， the
gastric emptying rate， small intestinal propulsion rate， the serum contents of MTL and GAS， and protein expression of p62 in
model group were all reduced significantly （P＜0.05）； the serum content of CCK， the co-localization expression of COX Ⅳ and
Parkin in mitochondria， the protein expressions of LC3， Pink1 and Parkin were all increased significantly （P＜0.05）. The number
of ICC mitochondria in gastric antrum tissue decreased， mitochondria became vacuolated， mitochondrial cristae were blurry， and
there were more autophagic lysosomes. Compared with the model group， the above indexes of the positive control group and the
Simo decoction group were reversed significantly （P＜0.05）； the mitochondrial structure of ICC gradually recovered， with clear
mitochondrial cristae and reduced autophagic lysosomes.
Δ 基金项目 湖南省自然科学基金项目（No.2022JJ70031）；湖南省 CONCLUSIONS Simotang oral liquid can improve
中医药科研计划项目（No.2021203）；湖南省中医重点专科（一类）（No.
gastrointestinal motility and gastrointestinal hormone levels in
湘中医药函〔2023〕4号）
＊第一作者 主治医师，硕士。研究方向：中医药防治消化系统疾 FD model rats， the mechanism of which may be related to
病。E-mail：253526775@qq.com inhibiting Pink1/Parkin axis and blocking autophagy.
# 通信作者 副主任医师，博士。研究方向：中医药防治消化系统 KEYWORDS Simotang oral liquid； PTEN-induced putative
疾病。E-mail：2396457091@qq.com kinase 1； E3 ubiquitin ligase； functional dyspepsia； autophagy

中国药房 2023年第34卷第21期 China Pharmacy 2023 Vol. 34 No. 21 · 2589 ·