白术根茎通过调节肠道屏障和水液代谢改善怀孕小鼠的胃肠道健康和妊娠结局。

The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via modulating intestinal barrier and water-fluid metabolism.

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.

出版信息

J Ethnopharmacol. 2024 May 23;326:117971. doi: 10.1016/j.jep.2024.117971. Epub 2024 Feb 24.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Baizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored.

AIM OF THE STUDY

This study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD).

METHODS

To simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin β (β-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated.

RESULTS

The results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (β-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

摘要

ETHNOPHARMACOLOGICAL 相关性:白术(BZ)是苍术(Compositae)的干燥根茎,能健脾益气,安胎,广泛用于治疗脾虚证。然而,BZ 对妊娠期间胃肠道功能的影响仍未得到探索。

研究目的

本研究阐明了 BZ 对脾虚腹泻(SDD)妊娠小鼠胃肠道健康和妊娠结局的改善作用。

方法

为了模拟不规则的人类饮食和过度摄入冷食和苦味食物导致的 SDD,使用隔日禁食和高脂肪饮食联合口服番泻叶建立 SDD 妊娠小鼠模型。在实验过程中,测量一般指标和腹泻相关参数。评估胃和肠道动力(小肠推进率和胃排空率)。使用酶联免疫吸附试验定量测定血清胃动素(MTL)、胃饥饿素、生长激素(GH)、胃泌素(Gas)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、绒毛膜促性腺激素β(β-CG)、孕酮(P)和雌二醇(E2)。通过苏木精和伊红染色(H&E)和阿尔辛蓝过碘酸希夫染色(AB-PAS)检查病理变化。通过免疫组织化学和免疫荧光测定结肠组织中肠道屏障和水代谢相关蛋白的表达水平。计算妊娠率、卵巢器官系数、带胎子宫器官系数、胎鼠体重小、平均胎重和体长。

结果

结果表明,BZ 显著改善了脾虚腹泻妊娠小鼠的一般指标和腹泻症状,提高了胃排空率和小肠推进率,升高了血清中胃肠激素(AMS、胃饥饿素、GH 和 Gas)水平,并降低了血脂水平(TC 和 LDL-c)。它还改善了结肠组织形态,增加了杯状细胞数量,并促进了结肠组织中 occludin、claudin-1、ZO-1、AQP3、AQP4 和 AQP8 的 mRNA 和蛋白表达,下调了 claudin-2 的 mRNA 和蛋白表达水平,从而减轻了肠道屏障损伤,调节了水和液体代谢平衡。BZ 还维持了脾虚腹泻妊娠小鼠血清中妊娠激素(β-CG、P 和 E2)的水平。此外,它提高了妊娠率、卵巢器官系数、带胎子宫器官系数、胎鼠窝产仔数、平均胎重和体长。这些发现表明,BZ 可以改善妊娠前和妊娠期间脾虚相关症状的妊娠小鼠,调节妊娠相关激素,并改善妊娠结局。

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