双术汤对大鼠的安全性及改善消化性不良的药效作用研究
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篇名: | 双术汤对大鼠的安全性及改善消化性不良的药效作用研究 |
TITLE: | Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats |
摘要: | 目的 研究双术汤对大鼠的安全性及其改善大鼠功能性消化不良(FD)的药效作用。方法安全性实验方面:取40只大鼠分为空白对照组和双术汤低、中、高剂量组[108、216、324g/(kg·d),以生药量计,下同],每天给予相应药物,连续14d;记录大鼠死亡情况、毒性反应,计算大鼠肝、肾、脾、肺、心的脏器指数,观察肝、肾、脾、肺、心、胃、十二指肠、结肠的病理形态学变化,以评估双术汤的急性毒性。另取40只大鼠同法分组、给药,连续30d;记录大鼠死亡情况、毒性反应,计算相应脏器指数,观察相应脏器病理形态学变化,检测血常规及血清生化指标水平,以评估双术汤的亚急性毒性。药效学实验方面:将50只大鼠分为空白对照组、模型组和双术汤低、中、高剂量组(9.45、18.9、37.8g/kg),每组10只;除空白对照组外,其余各组大鼠均通过皮下注射洛哌丁胺(3.5mg/kg)制备FD大鼠模型;各组大鼠灌胃相应药液/生理盐水,每天1次,连续14d。末次给药后,检测大鼠粪便含水率、小肠推进率、胃排空率和血清中胃动素水平,观察大鼠结肠组织中卡哈尔间质细胞(ICC)的超微结构。结果安全性实验结果显示:双术汤各剂量组大鼠均未出现死亡,脏器指数、血常规及血清生化指标水平与空白对照组比较,差异均无统计学意义(P>0.05),各脏器病理形态学观察未见异常。药效学实验结果显示:与空白对照组比较,模型组大鼠粪便含水率、胃排空率、小肠推进率、血清中胃动素水平均显著降低(P<0.05);结肠组织中ICC线粒体重度肿胀、嵴消失,内质网扩张。与模型组比较,双术汤高剂量组大鼠上述定量指标均显著升高(P<0.05);结肠组织中ICC有大量线粒体,且嵴清晰、排列规整。结论双术汤具有较好的安全性,且对FD大鼠具有较好的改善作用;其作用机制可能与调节胃肠激素表达以促进胃排空与肠推进,修复ICC线粒体结构以恢复胃肠功能有关。 |
ABSTRACT: | OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function. |
期刊: | 2025年第36卷第09期 |
作者: | 陈鑫源;熊常州;李炯汾;余康怡;徐欢;王樱遐;廖丹;陶俊宇;杨子仪;林才志 |
AUTHORS: | CHEN Xinyuan,XIONG Changzhou, LI Jiongfen,YU Kangyi,XU Huan,WANG Yingxia,LIAO Dan,TAO Junyu,YANG Ziyi,LIN Caizhi |
关键字: | 双术汤;安全性;药效学;急性毒性;亚急性毒性;消化性功能不良;胃肠动力障碍 |
KEYWORDS: | Shuangshu decoction; safety; pharmacodynamics; acute toxicity; subacute toxicity; functional dyspepsia; |
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