[芪止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]

摘要(中文译文)

帕金森病（PD）常伴有胃动力障碍症状，如胃轻瘫。胃轻瘫不仅严重影响PD患者的生活质量，还会导致药物吸收速率波动，加重PD的运动症状。本实验室前期研究表明，PD模型大鼠同样表现出胃轻瘫，胃肌层促炎细胞因子增加，相关神经元标志物异常。此外，平滑肌细胞（SMCs）中收缩蛋白标志物及其转录调节因子表达降低。连续胃饲七味白术散颗粒（QZWT）7天可通过抑制炎症改善PD胃轻瘫大鼠的胃动力。然而，QZWT能否恢复胃肌层神经元及SMCs的分化表型仍有待进一步研究。本研究采用免疫荧光染色、Western blotting和实时定量PCR检测胃肌层神经元标志物及SMCs收缩标志物的表达，并利用透射电子显微镜技术观察SMCs的超微结构，旨在探讨QZWT改善PD大鼠胃动力障碍的潜在机制，为PD胃轻瘫的治疗提供新思路。结果显示，给予QZWT后，PD胃轻瘫大鼠胃体肌层神经元标志物酪氨酸羟化酶、胆碱乙酰转移酶和神经元型一氧化氮合酶均无变化。然而，与PD大鼠相比，QZWT治疗的PD大鼠胃体平滑肌层中肌球蛋白重链11和肌球蛋白轻链20的蛋白及mRNA表达水平显著上调。此外，调控SMC收缩蛋白基因转录的血清反应因子（SRF）的蛋白及mRNA表达水平，以及转录相关辅因子心肌素（MYOCD）的mRNA水平均显著上调。另外，胃体超微结构特征显示，QZWT治疗的PD大鼠SMCs形态改善，致密斑和致密体清晰可见，SMCs内空泡消失。这些结果提示，QZWT治疗上调SRF和MYOCD的表达，这可能与其抑制炎症的作用相关，并进一步增加收缩蛋白的表达、恢复SMCs形态，促进PD胃轻瘫大鼠胃平滑肌收缩，从而改善胃动力。

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.

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Sheng li xue bao : [Acta physiologica Sinica] 的其他文献

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