1.甘肃中医药大学,甘肃省兰州市城关区定西东路35号,730000
2.甘肃中医药大学实验动物中心
3.宁夏医科大学中医学院
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收稿:2022-10-12,
修回:2023-01-31,
纸质出版:2023-07-02
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李润法,安耀荣,白敏等.香砂六君子汤对脾胃虚弱型功能性消化不良模型大鼠胃窦组织mTOR/ghrelin/GHSR-1a通路的影响[J].中医杂志,2023,64(13):1359-1365.
LI Runfa,AN Yaorong,BAI Min,et al.The Effect of Xiangsha Liujunzi Decoction (香砂六君子汤) on Regulating mTOR/ ghrelin/ GHSR-1a Pathway in Gastric Antrum Tissue of Functional Dyspepsia Rats with Spleen-stomach Weakness Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(13):1359-1365.
李润法,安耀荣,白敏等.香砂六君子汤对脾胃虚弱型功能性消化不良模型大鼠胃窦组织mTOR/ghrelin/GHSR-1a通路的影响[J].中医杂志,2023,64(13):1359-1365. DOI: 10.13288/j.11-2166/r.2023.13.012.
LI Runfa,AN Yaorong,BAI Min,et al.The Effect of Xiangsha Liujunzi Decoction (香砂六君子汤) on Regulating mTOR/ ghrelin/ GHSR-1a Pathway in Gastric Antrum Tissue of Functional Dyspepsia Rats with Spleen-stomach Weakness Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(13):1359-1365. DOI: 10.13288/j.11-2166/r.2023.13.012.
目的
2
探讨香砂六君子汤对脾胃虚弱型功能性消化不良(FD)模型大鼠胃排空的影响及可能作用机制。
方法
2
60只SD大鼠的乳鼠随机分为空白组、模型组、莫沙必利组和香砂六君子汤低、中、高剂量组,每组10只。除空白组外,其余各组大鼠采用碘乙酰胺联合蔗糖溶液灌胃+隔日给食+游泳力竭复制脾胃虚弱型FD大鼠模型。造模成功后香砂六君子汤高、中、低剂量组分别给予香砂六君子汤12、6、3 g/(kg·d)灌胃;莫沙必利组给予枸橼酸莫沙必利片1.35 mg/(kg·d)灌胃;空白组和模型组大鼠给予生理盐水10 ml/(kg·d)灌胃。连续干预2周后,测定各组大鼠体质量、胃排空率和肠推进率,HE染色观察各组大鼠胃组织病理学改变,检测大鼠胃窦组织中哺乳动物雷帕霉素靶蛋白(mTOR)、胃生长激素释放激素(ghrelin)、生长激素促分泌素受体1a(GHSR-1a)、c-kit蛋白表达和血浆酰基化胃生长激素释放激素(Acly-ghrelin)水平。
结果
2
与空白组比较,模型组大鼠体质量、胃排空率、肠推进率降低,胃窦组织中ghrelin、GHSR-1a、c-kit蛋白表达和血浆Acly-ghrelin水平均降低,mTOR蛋白表达升高(
P
<0.05)。与模型组比较,香砂六君子汤中、高剂量组和莫沙必利组大鼠体质量、胃排空率、肠推进率升高,胃窦组织中ghrelin、GHSR-1a、c-kit蛋白表达及血浆Acly-ghrelin水平均升高,mTOR蛋白表达降低(
P
<0.05)。与莫沙必利组比较,香砂六君子汤高剂量组大鼠胃窦组织中ghrelin蛋白表达升高,mTOR蛋白表达降低(
P
<0.05)。HE染色结果显示,各组大鼠胃组织病理形态学正常,腺体无萎缩,无炎性细胞浸润。
结论
2
香砂六君子汤中、高剂量能够显著促进脾胃虚弱型FD大鼠胃排空,其作用机制可能与香砂六君子汤可正向调控mTOR/ghrelin/GHSR-1a信号通路相关。
Objective
2
To explore the intervention effect and possible mechanism of
Xiangsha Liujunzi Decoction
(香砂六君子汤, XLD) in promoting gastric emptying in rats with functional dyspepsia (FD) of spleen-stomach weakness syndrome.
Methods
2
Sixty suckling SD rats were randomly divided into blank group, model group, mosapride group, low-, medium- and high-dose XLD groups, with 10 rats in each group. Except for the blank group, the rats in the other groups were gavaged with iodoacetamide (IA) and sucrose solution and administered with hunger diet plus swimming exhaustion to replicate the FD rat model of spleen-stomach weakness. After the model was successfully replicated, 12, 6 and 3 g/(kg·d) of XLD and 1.35 mg/(kg·d) of mosapride citrate tablets were given to the corresponding high-, medium and low-dose XLD groups and mosapride group by gavage, repectively, while 10 ml/(kg·d) of normal saline was administered by gavage in the blank group and model group. After two weeks of continuous intervention, the body weight of rats, gastric emptying rate and intestinal propulsion rate in each group were measured. The pathological changes of gastric tissue in each group were observed by hematoxylin and eosin (HE) staining. The levels of mammalian target of rapamycin (mTOR), gastric growth hormone releasing hormone (ghrelin), growth hormone secretagogue receptor 1a (GHSR-1a), and c-kit protein expression in gastric antrum and plasma acylated gastric growth hormone-releasing hormone (Acly-ghrelin) were detected.
Results
2
Compared to those in the blank group, the body weight of rats, gastric emptying rate, intestinal propulsion rate, the levels of ghrelin, GHSR-1a and c-kit protein expression in the gastric antrum tissue, and plasma Acly-ghrelin level significantly decreased, while the mTOR protein expression increased in the model group (
P
<0.05). Compared to those in the model group, the body weight, gastric emptying rate, intestinal propulsion rate and the levels of ghrelin, GHSR-1a and c-kit protein expression in gastric antrum tissue and plasma Acly-ghrelin of rats in the high- and medium-dose XLD group and mosapride group significantly increased, while the level of mTOR protein significantly decreased (
P
<0.05). Compared to the mosapride group, the high-dose XLD group had increased ghrelin protein expression in the gastric antrum tissue and decreased mTOR protein expression (
P
<0.05
).
HE staining showed that the pathological morphology of the gastric tissues of rats in each group was normal, and the glands did not atrophy, with no inflammatory cell infiltration.
Conclusion
2
Medium- and high-dose XLD can significantly improve gastric emptying in FD rats with spleen-stomach weakness. The mechanism may be related to the positive regulation of mTOR/ ghrelin/ GHSR-1a signaling pathway by XLD.
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