玉竹醇提取物B调控免疫代谢抗结直肠癌的药理机制研究

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

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。方法将25只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及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。

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 mediumdose group,and then the low-dose group.Peripheral blood levels of IL-2,IL-12 and TNF-αwere 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-αas compared with the CRC model group(P<0.05),and levels of three indicators were the highest in the high-dose group,followed by the medium-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 polygonatum odoratum may play an anticancer role by reducing colorectal tumor number and hyperplasia through regulating immunometabolism.