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气滞胃痛颗粒改善帕金森病胃轻瘫大鼠胃平滑肌细胞的收缩表型

张悦¹, 修晓琳¹, 沈倩影¹, 刘子名^1,2, 孙雨丽^1,3, 张晓丽¹, 朱进霞¹, 郑丽飞^1,*

¹首都医科大学基础医学院生理学与病理生理学学系，北京 100069；²中国康复研究中心病理科，北京 100068；³首都医科大学附属北京积水潭医院核医学科，北京 100035

摘要

帕金森病(Parkinson's disease, PD)常伴有胃轻瘫等胃动力不足的表现。胃轻瘫不仅严重影响PD患者的生活质量，还可引起药物吸收速率的波动，加重PD运动症状。本研究组前期研究发现，PD模型大鼠同样表现出胃轻瘫，其胃体肌层促炎因子增加，相关神经元的标志物异常，平滑肌细胞(smooth muscle cell, SMC)中收缩蛋白标志物及其转录调控因子均降低。持续7 天灌胃气滞胃痛颗粒(Qizhiweitong particles, QZWT)可通过抑制炎症改善PD胃轻瘫大鼠的胃动力，但QZWT是否能改善胃体肌层神经元、恢复SMC分化表型，有待进一步研究。本文通过免疫荧光染色、蛋白免疫印迹和实时定量PCR技术检测胃体肌层神经元标志物及SMC收缩相关指标的变化，通过透射电镜观察SMC超微结构，旨在探究QZWT改善PD大鼠胃动力的可能机制，以期为治疗PD胃轻瘫提供新的思路。结果显示，QZWT治疗后，PD胃轻瘫大鼠胃体肌层中胆碱乙酰转移酶、酪氨酸羟化酶、神经型一氧化氮合酶的表达并未改善，但胃体SMC中肌球蛋白轻链20 和肌球蛋白重链11 mRNA和蛋白表达水平均显著上调。进一步研究发现，血清反应因子(serum response factor, SRF)蛋白和mRNA水平，以及转录相关辅助因子心肌素(myocardin, MYOCD) mRNA表达水平均明显上调。胃体SMC的超微形态出现好转，其密斑、密体清晰可见，胞内空泡基本消失。以上结果提示，QZWT可抑制胃体肌层炎症，上调SRF和MYOCD表达，上调胃体SMC的收缩蛋白表达，改善SMC形态结构，从而提高PD胃轻瘫大鼠胃平滑肌收缩能力，改善胃动力。

关键词： 帕金森病胃轻瘫; 气滞胃痛颗粒; 胃平滑肌细胞; 血清反应因子; 收缩蛋白

Qizhiweitong particles improve the contractile phenotype of gastric smooth muscle cells in the Parkinson's disease rats with gastroparesis

ZHANG Yue¹, XIU Xiao-Lin¹, SHEN Qian-Ying¹, LIU Zi-Ming^1,2, SUN Yu-Li^1,3, ZHANG Xiao-Li¹, ZHU Jin-Xia¹, ZHENG Li-Fei^1,*

¹Department of Physiology and Pathophysiology, College of Basic Medical Sciences, Capital Medical University, Beijing 100069, China；²Department of Pathology, China Rehabilitation Research Center, Beijing 100068, China；³Department of Nuclear Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing 100035, China

Abstract

Parkinson's disease (PD) is often accompanied by symptoms of gastric dysmotility, such as gastroparesis. Gastroparesis not only seriously affects the life quality of PD patients, but also causes fluctuations in drug absorption rate, exacerbating the motor symptoms of PD. The previous studies of our laboratory have shown that PD model rats also exhibit gastroparesis, with increased pro-inflammatory cytokines in the gastric muscularis. The markers of related neurons were abnormal. Additionally, the contractile protein markers, as well as their transcriptional regulators, were reduced in smooth muscle cells (SMCs). Continuous gastric feeding of Qizhiweitong particles (QZWT) for seven days improved gastric motility in PD rats with gastroparesis by suppressing inflammation. However, whether QZWT can restore neurons in the gastric muscularis and the differentiated phenotype of SMCs remains to be further investigated. In this study, we detected expressions of neuronal markers in the gastric muscularis and contractile markers of SMCs by immunofluorescence staining, Western blotting, and real-time quantitative PCR, and observed the ultrastructure of SMCs by transmission electron microscopy techniques, aiming to explore the potential mechanisms underlying the improvement effect of QZWT on gastric dysmotility in PD rats and provide new ideas for the treatment of PD gastroparesis. Our results showed that after QZWT administration, there was no change in neuronal markers tyrosine hydroxylase, choline acetyltransferase, and neuronal nitric oxide synthase in the muscular layer of gastric corpus of the PD gastroparesis rats. However, compared to the PD rats, the protein and mRNA expression levels of myosin heavy chain 11 and myosin light chain 20 were significantly up-regulated in the smooth muscle layer of gastric corpus of PD rats with QZWT treatment. Furthermore, the protein and mRNA expression levels of serum response factor (SRF), which regulates the transcription of SMC contractile protein genes, as well as the mRNA level of the transcription related cofactor myocardin (MYOCD), were significantly up-regulated. In addition, the ultrastructure feature of gastric corpus showed that the morphology of SMCs in the PD rats with QZWT treatment was improved, displaying clear dense patches and dense bodies. The vacuoles in the SMCs disappeared. These results suggest that QZWT treatment up-regulates the expression of SRF and MYOCD, which may be associated with its effect of inhibiting inflammation, and further increases the expression of contractile proteins and restores the morphology of the SMCs, promoting gastric smooth muscle contractions in PD gastroparesis rats, thereby leading to improved gastric motility.

Key words: Parkinson''s disease gastroparesis; Qizhiweitong particles; gastric smooth muscle cells; serum response factors; contractile proteins

收稿日期：　　录用日期：

通讯作者：郑丽飞　　E-mail:

DOI: 10.13294/j.aps.2025.0104

引用本文：

张悦, 修晓琳, 沈倩影, 刘子名, 孙雨丽, 张晓丽, 朱进霞, 郑丽飞. 气滞胃痛颗粒改善帕金森病胃轻瘫大鼠胃平滑肌细胞的收缩表型[J]. 生理学报 2026; 78 (3): 605-615.

ZHANG Yue, XIU Xiao-Lin, SHEN Qian-Ying, LIU Zi-Ming, SUN Yu-Li, ZHANG Xiao-Li, ZHU Jin-Xia, ZHENG Li-Fei. Qizhiweitong particles improve the contractile phenotype of gastric smooth muscle cells in the Parkinson's disease rats with gastroparesis. Acta Physiol Sin 2026; 78 (3): 605-615 (in Chinese with English abstract).