周立1,2, 姚元生1, 张晓丽1, 郑丽飞1, 朱进霞1,*
1首都医科大学基础医学院生理学与病理生理学系，北京 100069；2新乡医学院人体解剖学与组织胚胎学系，新乡 453003
本文旨在研究气滞胃痛颗粒(Qizhiweitong particles, QZWT)对胃轻瘫模型大鼠胃动力的影响，为其临床治疗提供理论与实验依据。选用SPF级雄性Sprague-Dawley (SD)大鼠，双侧中脑黑质注射6-羟基多巴胺建立胃轻瘫大鼠模型，单次胃饲1、10、30、100、200、450或675 mg/kg QZWT或连续7天每天胃饲675 mg/kg QZWT，用胃固体食物排空实验和在体X线成像技术检测胃排空率，用PowerLab生物信号采集系统检测离体和在体胃体纵行肌收缩，用植入式生理信号无线遥测系统检测胃肌电活动，用蛋白免疫印迹检测胃肌层促炎蛋白酶表达水平。结果显示，QZWT单次给药可剂量依赖性地抑制正常大鼠离体胃平滑肌的收缩活动。QZWT单次给药抑制对照和模型组大鼠在体胃动力及胃肌电活动。与对照组相比，模型组大鼠的胃排空率、在体和离体胃动力以及胃肌电活动均显著降低，QZWT连续给药可改善模型组大鼠上述胃动力指标。QZWT单次给药抑制离体胃肌条收缩，阿托品和一氧化氮合酶抑制剂预处理均对此作用无影响。QZWT连续给药可下调模型组大鼠升高了的一氧化氮合酶和环氧合酶2的蛋白表达水平。上述结果提示，临床上QZWT缓解胃痛的作用可能与其抑制胃动力的即刻作用有关，与乙酰胆碱和一氧化氮通路无关。QZWT长期治疗可增强胃肌电活动、促进胃平滑肌收缩和胃排空，从而改善胃动力，其作用机制可能部分与炎症抑制有关。
关键词： 气滞胃痛颗粒; 胃轻瘫; 胃动力; 胃肌电; 胃轻瘫模型大鼠
Dual regulation of Qizhiweitong particles on gastric motility in the model rats with gastroparesis
ZHOU Li1,2, YAO Yuan-Sheng1, ZHANG Xiao-Li1, ZHENG Li-Fei1, ZHU Jin-Xia1,*
1Department of Physiology and Pathophysiology, College of Basic Medical Sciences, Capital Medical University, Beijing 100069, China；2Department of Human Anatomy and Histoembryology, Xinxiang Medical University, Xinxiang 453003, China
This paper was aimed to study the effects of Qizhiweitong particles (QZWT) on gastric motility in gastroparesis model rats, and to provide a theoretical and experimental basis for its clinical treatment. Rat gastroparesis model was established by bilateral injection of 6-hydroxydopamine into the substantia nigra in male Sprague-Dawley (SD) rats. The model rats received single gastric feeding of 1, 10, 30, 100, 200, 450, or 675 mg/kg QZWT or continuous administration of 675 mg/kg QZWT per day for 7 days. The gastric motility was measured by gastric emptying study and in vivo digital X-ray imaging system. The in vivo and ex vivo gastric longitudinal muscle contraction was recorded by PowerLab biological signal acquisition system. Gastric myoelectric signals were recorded by wireless implantable telemetry system. Protein expression levels of proinflammatory proteases in the myometrium were determined by Western blot. The results showed that the single administration of QZWT dose-dependently inhibited the contractile activity of isolated gastric strips from normal rats. The single administration of QZWT inhibited the in vivo contraction of gastric smooth muscle and gastric myoelectric signal in the control and model rats. The gastric emptying rate, in vivo and ex vivo gastric motility and gastric myoelectric signal in the model rats were significantly decreased compared with those in the control rats; While the continuous administration of QZWT markedly improved all the above indices of gastric motility function. The single administration of QZWT inhibited isolated gastric muscle strip contraction, and neither atropine nor nitric oxide synthase inhibitor pretreatments affected QZWT’s inhibitory effects. The continuous administration of QZWT down-regulated the increased protein expression levels of nitric oxide synthase and cyclooxygenase 2 in the model group. These results suggest that, in clinical treatment, the single administration of QZWT may induce an analgesic effect by rapidly inhibiting gastric motility, while this effect is not related to acetylcholine or nitric oxide pathways. Long-term treatment with QZWT may ameliorate gastric motility through enhancing myoelectric activities, gastric smooth muscle contraction and gastric emptying, and this effect may partly be related to its anti-inflammatory effect.
Key words: Qizhiweitong particles; gastroparesis; gastric motility; gastric myoelectric activity; gastroparesis model rats
通讯作者：朱进霞 E-mail: firstname.lastname@example.org
周立, 姚元生, 张晓丽, 郑丽飞, 朱进霞. 气滞胃痛颗粒双向调节胃轻瘫模型大鼠的胃动力[J]. 生理学报 2022; 74 (5): 685-696.
ZHOU Li, YAO Yuan-Sheng, ZHANG Xiao-Li, ZHENG Li-Fei, ZHU Jin-Xia. Dual regulation of Qizhiweitong particles on gastric motility in the model rats with gastroparesis . Acta Physiol Sin 2022; 74 (5): 685-696 (in Chinese with English abstract).