实用医学杂志 ›› 2022, Vol. 38 ›› Issue (15): 1908-1912.doi: 10.3969/j.issn.1006⁃5725.2022.15.011

• 基础研究 • 上一篇    下一篇

玉竹醇提取物B 药理机制研究调控免疫代谢抗结直肠癌的 

赵守彰1 马强2 权冬梅2    

  1. 1 辽宁医药职业学院(沈阳110101);2 沈阳市第六人民医院中西医结合肝病科(沈阳110006)


  • 出版日期:2022-08-10 发布日期:2022-08-10
  • 基金资助:
    国家自然科学基金(编号:81803860)

Pharmacological mechanism of ethanol extract B from polygonatum odoratum against colorectal cancer via regulating immunometabolism

ZHAO Shouzhang*,MA Qiang,QUAN Dongmei.    

  1. Liaoning Vocational College of Medicine,Shenyang 110101,China 

  • Online:2022-08-10 Published:2022-08-10

摘要:

目的 研究玉竹醇提取物 B 调控免疫代谢抗结直肠癌(CRC)的药理机制。方法 25 实验小鼠分为空白对照组、CRC 模型组及 CRC+不同浓度玉竹醇提取物 B 处理组(低剂量组、中剂量组、高 剂量组),CRC+不同浓度玉竹醇提取物 B 处理组小鼠分别给予 1、2、3 g/kg 玉竹醇提取物 B 腹腔注射,空白 对照组及 CRC 模型组给予等体积生理盐水腹腔注射,连续给药 8 周后,检测各组大鼠外周血 NK 细胞杀伤 活性、白细胞介素⁃2(IL⁃2)、肿瘤坏死因子⁃α(TNF⁃α)浓度,处死大鼠,计算其脏器指数,观察结直肠肿瘤 形成情况。结果 CRC模型组小鼠血液中NK细胞对靶细胞的杀伤活性明显低于空白对照组,而不同浓度 玉竹醇提取物 B 组小鼠 NK 细胞对靶细胞的杀伤活性较模型组升高,其中中剂量组 NK 细胞杀伤活性高于 低剂量组,高剂量组NK细胞杀伤活性高于中剂量组。与空白对照组相比,模型组小鼠外周血IL⁃2、IL⁃12 TNF⁃α 水平均下降,差异具有统计学意义(P < 0.05),而与模型组小鼠相比,不同浓度玉竹醇提取物 B 组小 鼠血清IL⁃2、IL⁃12以及TNF⁃α水平均上升,其中中剂量组血清IL⁃2、IL⁃12以及TNF⁃α水平高于低剂量组,高 剂量组血清 IL⁃2、IL⁃12 以及 TNF⁃α 水平高于中剂量组,差异均具有统计学意义(P < 0.05)。模型组与玉竹 醇提取物B组心脏及肝脏等指数比较,差异均无统计学意义(P > 0.05),但不同浓度玉竹醇提取物B组脾脏 指数及胸腺指数均较模型组高,其中中剂量组脾脏及胸腺指数高于低剂量组,高剂量组脾脏及胸腺指数高 于中剂量组,差异均具有统计学意义(P < 0.05)。解剖发现,模型组小鼠结直肠中可见肿瘤与其他异常增 生,而经不同浓度玉竹醇提取物 B 处理后的 CRC 模型小鼠结直肠中肿瘤与其他异常增生数目明显减少 [(8.83 ± 0.71)vs.(4.68 ± 0.46)vs.(3.41 ± 0.78)vs.(2.13 ± 0.53),F = 65.642,P < 0.001]。结论 玉竹醇提 取物B可能通过调节免疫代谢减少CRC结直肠肿瘤数目及异常增生,发挥抗癌作用。

关键词:

结直肠癌, 玉竹醇提取物B, 免疫代谢, 药理机制研究

Abstract:

Objective To explore the pharmacological mechanism of ethanol extract from polygonatum odoratum against colorectal cancer(CRC)via regulating immunometabolism. Methods Twenty ⁃five mice were divided into a blank control group,CRC model group and CRC + polygonatum odoratum ethanol extract treatment group. The mice in CRC + polygonatum odoratum ethanol extract treatment group received intraperitoneal injection of polygonatum odoratum ethanol extract at a concentration of 1 g/kg,2 g/kg,or 3 g/kg,respectively,while mice in the blank control group and the CRC model group received intraperitoneal injection of equal volume of normal saline. After 8 weeks of continuous administration,peripheral blood NK cell killing activity and levels of interleukin ⁃2(IL⁃2),interleukin⁃12(IL⁃12)and tumor necrosis factor⁃α(TNF⁃α)were measured in each group. Organ indexes were calculated and colorectal tumor formation was observed. Results The peripheral blood NK cell killing activity was significantly lower in the CRC model group than in the blank control group. After treatment with polygonatum odoratum ethanol extract,the NK cell killing activity was significantly enhanced as compared with that in the CRC model group(P < 0.05),having the highest level in the high⁃dose group,followed by the medium⁃ dose group,and then the low⁃dose group. Peripheral blood levels of IL⁃2,IL⁃12 and TNF⁃ α were significantly decreased in the CRC model group as compared with those in the blank control group(P < 0.05),while polygonatum odoratum ethanol extract significantly up⁃regulated serum levels of IL⁃2,IL⁃12 and TNF⁃α as compared with the CRC model group(P < 0.05),and levels of three indicators were the highest in the high⁃dose group,followed by themedium⁃dose group,and were the lowest in the low⁃dose group(P < 0.05). Cardiac and liver indexes did not differ statistically between the CRC model group and the polygonatum odoratum ethanol extract treatment group(P > 0.05),while the indexes of spleen and thymus in the polygonatum odoratum ethanol extract treatment group were significantly increased as compared with those in the model group(P < 0.05),and the increase was the most significant in the high⁃dose group,followed by the medium⁃dose group,and was the least in the low⁃dose group (P < 0.05). Anatomical experiments showed that tumor and other abnormal hyperplasia were observed in colon and rectum in the model group,while the number of tumor and other abnormal hyperplasia was significantly reduced after treatment with polygonatum odoratum ethanol extract at different concentrations[(8.83 ± 0.71)vs.(4.68 ± 0.46)vs.(3.41 ± 0.78)vs.(2.13 ± 0.53),F = 65.642,P < 0.001]. Conclusions Ethanol extract from polygona⁃ tum odoratum may play an anticancer role by reducing colorectal tumor number and hyperplasia through regulating immunometabolism.

Key words:

colorectal cancer, polygonatum odoratum ethanol extract, immunometabolism, pharma? cological mechanism study