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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

Received: 　　Accepted:

Corresponding author: 郑丽飞　　E-mail:

DOI: 10.13294/j.aps.2025.0104

Citing This Article：

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).