五味子乙素对胶质瘤大鼠新辅助化疗敏感性的影响

Effect of Schisandrin B on sensitivity to neoadjuvant chemotherapy in rats with glioma

目的评价五味子乙素对胶质瘤大鼠新辅助化疗敏感性的影响。方法健康雄性Wistar大鼠72只,体重180~200 g,采用随机数字表法分为6组(n=12):假手术组(Sham组)、胶质瘤组(G组)、新辅助化疗组(T组)、五味子乙素10 mg/kg+新辅助化疗组(S1+T组)、五味子乙素20 mg/kg+新辅助化疗组(S2+T组)和五味子乙素40 mg/kg+新辅助化疗组(S3+T组)。右侧尾状核区注射10μl C6胶质瘤细胞悬液,制备胶质瘤模型。T组于造模后10 d时给予替莫唑胺25 mg/kg灌胃,连续6 d;S1+T组、S2+T组、S3+T组于造模后10 d时分别给予五味子乙素10、20、40 mg/kg和替莫唑胺25 mg/kg灌胃,连续6 d。于造模后18 d时,每组取6只大鼠,剥离瘤体并称重;取瘤体核心区组织,采用Western blot法检测基质金属蛋白-2(MMP-2)、MMP-9和谷胱甘肽过氧化物酶(GPX4)表达水平。其余6只大鼠记录生存时间。结果与Sham组比较,其余5组生存时间缩短,瘤体组织MMP-2、MMP-9和GPX4的表达上调(P<0.05);与G组比较,T组、S1+T组、S2+T组、S3+T组瘤体重量下降,生存时间延长,瘤体组织MMP-2、MMP-9和GPX4的表达下调(P<0.05);与T组比较,S1+T、S2+T组和S3+T组瘤体重量下降,生存时间延长,瘤体组织MMP2、MMP9和GPX4表达下调(P<0.05);与S2+T组比较,S1+T组和S3+T组瘤体重量升高,生存时间缩短,瘤体组织MMP2、MMP9和GPX4的表达上调(P<0.05);S1+T组和S3+T组上述各指标比较差异无统计学意义(P>0.05)。结论五味子乙素可增强胶质瘤大鼠新辅助化疗的敏感性,可能与抑制肿瘤侵袭转移和促进铁死亡有关,其中20 mg·kg^(-1)·d^(-1)效果最佳。

Objective To evaluate the effect of Schisandrin B(Sch B)on the sensitivity to neoadjuvant chemotherapy in rats with glioma.Methods Seventy-two healthy male Wistar rats,weighing 180-200 g,were divided into 6 groups(n=12 each)using a random number table method:sham operation group(group Sham),glioma group(group G),neoadjuvant chemotherapy group(group T),Sch B 10 mg/kg plus neoadjuvant chemotherapy group(group S1+T),Sch B 20 mg/kg plus neoadjuvant chemotherapy group(group S2+T),and Sch B 40 mg/kg plus neoadjuvant chemotherapy group(group S3+T).C6 glioma cell suspension 10μl was injected into the right caudate nucleus to establish the glioma model.Temozolomide 25 mg/kg was given intragastrically starting from the 10th day after establishing the model for 6 consecutive days in group T.Sch B 10,20 and 40 mg/kg and temozolomide 25 mg/kg were given intragastrically starting from the 10th day after establishing the model for 6 consecutive days in S1+T,S2+T and S3+T groups,respectively.At 18 days after the model was established,6 rats from each group were selected,and the tumors were isolated and weighed.The core area of tumors was removed to detect the expression of matrix metalloprotein-2(MMP-2),MMP-9 and glutathione peroxidase(GPX4)using Western blot.The survival time of rats left in each group was recorded.Results Compared with group Sham,the survival time was significantly shortened,and the expression of MMP2,MMP9 and GPX4 was up-regulated in the other five groups(P<0.05).Compared with group G,the weight of glioma was significantly decreased,the survival time was prolonged,and the expression of MMP2,MMP9 and GPX4 was down-regulated in T,S1+T,S2+T and S3+T groups(P<0.05).Compared with group T,the weight of glioma was significantly decreased,the survival time was prolonged,and the expression of MMP2,MMP9 and GPX4 was down-regulated in S1+T,S2+T and S3+T groups(P<0.05).Compared with group S2+T,the weight of glioma was significantly increased,the survival time was shortened,and the expression of MMP2,MMP9 and GPX4 was up-regulated in S1+T and S3+T groups(P<0.05).There was no significant difference in the parameters mentioned above between group S1+T and group S3+T(P>0.05).Conclusion Schisandrin B can enhance the sensitivity to neoadjuvant chemotherapy in rats with glioma,which may be related to inhibition of tumor invasion and metastasis and promotion of ferroptosis,and 20 mg·kg^(-1)·d^(-1) has the best effect.