摘要
目的探讨素养汤(西兰花和紫甘蓝,SYZ)预防治疗大鼠胃癌的药效学及机制。方法90只SD大鼠随机分为正常对照组,30%醋酸+甲基硝基亚硝基胍(MNNG组),MNNG+环磷酰胺(CY)组,MNNG+SYZ 5、10、20 g/kg组,每组15只。造模前1 d,SYZ开始灌胃给药(qd);造模第6周开始每隔2 d腹腔注射给药CY 200 mg/kg,直至第25周时处死全部大鼠。观察大鼠一般情况;体重、死亡率、成瘤等。流式细胞术检测T细胞的总数;Western blot检测水通道蛋白4(AQP4)、B细胞淋巴瘤/白血病-2基因(Bcl-2)、半胱天冬酶3(Caspase-3)、Caspase-9的蛋白表达。结果MNNG组大鼠活动减少,倦怠,精神不佳,食欲减少,MNNG+CY和MNNG+SYZ组显著得到改善。MNNG、MNNG+CY、MNNG+SYZ 5 g/kg、MNNG+SYZ 10 g/kg、MNNG+SYZ 20 g/kg组大鼠死亡率分别为53.3%、46.6%、53.3%、40.0%、33.3%。MNNG+CY、MNNG+SYZ 5 g/kg、MNNG+SYZ 10 g/kg、MNNG+SYZ 20 g/kg组大鼠体重分别为523、200、325、401 g,均高于MNNG组的125 g,差异有统计学意义(P<0.05)。与MNNG组比较,MNNG+CY、MNNG+SYZ10 g/kg、MNNG+SYZ 20 g/kg组增生、溃疡浸润减少,HE显示出现少量的炎症细胞。MNNG组脾脏和淋巴结中Treg细胞总数(6.91±0.27)×105、(9.40±0.74)×105,均高于正常对照组(4.08±0.27)×105、(5.19±0.45)×105,差异有统计学意义(P<0.05);MNNG+CY组(4.70±0.41)×105、(6.65±0.52)×105,MNNG+SYZ 10 g/kg组(5.97±0.47)×105、(7.70±0.66)×105,MNNG+SYZ 20 g/kg组(4.99±0.36)×105、(7.73±0.86)×105较MNNG组降低,差异均有统计学意义(P<0.05)。与正常对照组大鼠比较,MNNG组大鼠组织的AQP4,Caspase-3、9,PARP的表达降低,Bcl-2表达增高,差异有统计学意义(P<0.05);MNNG+CY、MNNG+SYZ 10 g/kg、MNNG+SYZ 20 g/kg组AQP4,Caspase-3、9,PARP较MNNG组升高,Bcl-2较MNNG组降低,差异均有统计学意义(P<0.05)。结论SYZ 10和20 g/kg预防给药能有效保护/改善大鼠胃癌,其机制可能是通过抑制Bcl-2,激活Caspase-9、3通路诱导肿瘤细胞凋亡。
Objective To explore the pharmacodynamics and mechanism of SuYang Decoction(SYZ,Broccoli and Purple cabbage)in the prevention and treatment of gastric cancer in rats.Methods 90 SD rats were randomly divided into PBS,30%acetic acid+methylnitroguanidine(MNNG),MNNG+cyclophosphamide(CY),MNNG+SYZ 5,10,20 g/kg treatment groups(15/group).SYZ was used into intragastric administrated(qd)at one day before the modeling.Cy(200 mg/kg)was injected in the MNNG group every two days from the 6th week.All rats were anesthesiaed and killed at the 25 th week.Weight,mortality,tumor formation of rats were recorded in all process.The total number of T cells was measured by flow cytometry.Protein expressions of aquaporins 4(AQP4),B-cell lymphoma-2(Bel-2),Caspase-3 and 9 were detected by Western blot.Results The rats in MNNG group had reduced activity,burnout,poor mentality,and decreased appetite.The rats in MNNG+CY and MNNG+SYZ treatment groups-were significantly improved.The death rates of MNNG,MNNG+CY,MNNG+SYZ 5 g/kg,MNNG+SYZ 10 g/kg,MNNG+SYZ 20 g/kg groups were 533%,46.6%,53.3%,40.0%,and33.3%,respectively.The weights of rats in MNNG+CY,MNNG+SYZ 5 g/kg,MNNG+SYZ 10 g/kg,and MNNG+SYZ 20 g/kg groups were 523,200,325,and 401 g,respectively,which were all higher than 125 g in the MNNG group.Compared with the MNNG group,the rats in MNNG+CY,MNNG+SYZ 10 and 20 g/kg groups had reduced proliferation and ulcer infiltration,and HE shewed a small amount of inflammatory cells.The total number of Treg cells in the spleen and lymph nodes of the MNNG group was(6.91±0.27)×105 and(9.40±0.74)×105,respectively,which were significantly higher than those in the normal group(4.08±0.27)×105 and(5.19±0.45)×105(P<0.05).The total number of Treg cells in the spleen and lymph nodes of the MNNG+CY group(4.70±0.41)×105,(6.65±0.52)×105,MNNG+SYZ 10 g/kg group(5.97±0.47)×105,(7.70±0.66)×105,MNNG+SYZ 20 g/kg group(4.99±0.36)×105,(7.73±0.86)×105 was significantly lower than those of the MNNG group(P<0.05).The levels of AQP4,Caspase-3,9,and PARP in the MNNG+CY,MNNG+SYZ 10 g/kg,MNNG+SYZ 20 g/kg groups were increased when compared with those in the MNNG group,while the Bel-2 levels were decreased(P<0.05).Conclusion SYZ 10,20 g/kg could effectively protect and improve gastric cancer in rats through inhibition of Bcl-2 and Caspase activity.
作者
高擎
葛亚中
谢家翠
周晓琴
周毅
GAO Qing;GE Ya-zhong;XIE Jia-cui;XIAO Xiao-qin;ZHOU Yi(Department of Healthy Food Development,Infinitus(China)Company Ltd.,Guangzhou,Guangdong 510024;Department of Pharmacology,College of Pharmaceutical Science,Guangzhou Medical University,Guangzhou,Guangdong 511436,China)
出处
《热带医学杂志》
CAS
2020年第1期18-22,145,共6页
Journal of Tropical Medicine
基金
校企联合项目(GZ201612354).
