摘要
目的观察平消胶囊对实验性乳腺癌的作用。方法将36只SD雌性大鼠随机分为6组:正常组、模型组、他莫昔芬组(0.36 mg/kg)以及平消胶囊低(250 mg/kg)、中(500 mg/kg)、高(750 mg/kg)剂量组。采用腹腔注射二甲基苯蒽(DMBA,80 mg/kg)的方法建立大鼠乳腺癌模型,建模3 d后给予药物干预,正常组大鼠给予正常饮食,25周后观察乳腺肿瘤发生情况及进行组织病理学分析;并用酶联免疫吸附试验(ELISA)检测大鼠血清中雌二醇(E_(2))、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子α(TNF-α)水平变化;观察大鼠脏器指数的变化。多组间比较采用单因素方差分析,重复测量数据采用重复测量的方差分析,两两比较采用LSD法。结果(1)大鼠体质量经重复测量方差分析显示,时间因素、分组因素以及时间与分组的交互作用均对大鼠体质量有影响(F=70.385,P<0.001;F=19.389,P<0.001;F=3.184,P=0.020)。(2)模型组大鼠双侧乳腺均发生肿瘤,给予他莫昔芬及平消胶囊干预后,大鼠只发生单侧乳腺肿瘤;模型组乳腺肿瘤体积为(21.5±9.6)cm^( 3),他莫昔芬组及平消胶囊低、中、高剂量组乳腺肿瘤体积分别为(13.6±9.6)、(20.1±5.3)、(15.5±6.2)、(5.2±2.3)cm^( 3),其中高剂量组乳腺肿瘤体积与模型组比较,差异有统计学意义(P<0.050)。(3)各组大鼠双侧第二乳头直径的差异有统计学意义(右侧:F=11.378,P<0.001;左侧:F=9.600,P<0.001),组间两两比较显示:模型组分别与他莫昔芬组以及平消胶囊中、高剂量组比较,差异均有统计学意义(P均<0.050);他莫昔芬组与平消胶囊低剂量组比较,差异也有统计学意义(P<0.050)。(4)各组大鼠血清中E_(2)、GSH-Px、SOD、MDA、TNF-α水平差异均有统计学意义(F=64.845、60.303、32.583、80.558、46.740,P均<0.001)。其中,模型组与正常组比较,E_(2)、MDA、TNF-α水平明显升高(P均<0.050),GSH-Px、SOD水平明显降低(P均<0.050);模型组分别与他莫昔芬组、平消胶囊中剂量及高剂量组比较,E_(2)、GSH-Px、SOD、MDA、TNF-α水平的差异均有统计学意义(P均<0.050),他莫昔芬组分别与平消胶囊中、高剂量组比较,E_(2)、GSH-Px、SOD、MDA水平的差异均有统计学意义(P均<0.050)。(5)各组间子宫、胸腺、脾脏、肝脏及肾脏脏器指数的差异均有统计学意义(F=3.502、1.696、13.672、2.995、4.465,P均<0.050),其中,模型组分别与正常组、他莫昔芬组以及平消胶囊中、高剂量组比较,子宫、胸腺、脾脏脏器指数的差异均有统计学意义(P均<0.050),他莫昔芬组分别与平消胶囊低、中、高剂量组比较,差异均无统计学意义(P均>0.050)。HE染色结果显示,平消胶囊中、高剂量组大鼠的乳腺瘤样变化程度减轻,腺泡数量减小,导管增生和扩张也有明显改善,病变明显减轻。结论平消胶囊对DMBA诱导的大鼠乳腺癌病变具有显著的防治作用,其作用机制可能与其调节血清中E_(2)、GSH-Px、SOD、MDA、TNF-α水平,调节机体氧化应激状态,进而提高机体免疫调节水平有关。
Objective To observe the effect of Pingxiao capsules on experimental breast cancer.Methods The 36 female SD rats were randomly divided into 6 groups:normal group,model group,tamoxifen group(0.36 mg/kg),low-dose Pingxiao capsule group(250 mg/kg),medium-dose group(500 mg/kg)and high-dose group(750 mg/kg).The rat model of breast cancer was established by intraperitoneal injection of 7,12-dimethylbenz[a]anthracene(DMBA,80 mg/kg).After 3 days,the rats had normal diet in normal group,while the rats were given drug intervention in other groups.After 25 weeks,the rats were observed for breast tumor and histopathological analysis was performed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of estradiol(E_(2)),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),malondialdehyde(MDA)and tumor necrosis factor α(TNF-α)in serum of rats.The changes of viscera mass index in rats were observed.The analysis of variance(ANOVA)was used for comparison among multiple groups,and the LSD method was used for pairwise comparison.Repeated measurement data were analyzed by repeated measures of ANOVA.Results(1)The repeated measures of ANOVA showed that time,grouping and interaction between time and grouping all affected body weight of rats(F=70.385,P<0.001;F=19.389,P<0.001;F=3.184,P=0.020).(2)The rats in model group had bilateral breast tumors,while the rats only had unilateral breast tumor after intervention of tamoxifen and Pingxiao capsules.The tumor volume in model group was(21.5±9.6)cm^( 3).The breast tumor volume was(13.6±9.6),(20.1±5.3),(15.5±6.2),(5.2±2.3)cm^( 3) in tamoxifen group,low-dose Pingxiao capsule group,medium-dose group and high-dose group,respectively.The breast tumor volume presented a significant difference between high-dose group and model group(P<0.050).(3)The diameter of bilateral second nipples presented a significant difference among groups(right:F=11.378,P<0.001;left:F=9.600,P<0.001).Pairwise comparison showed that there were significant differences between model group and tamoxifen group/medium-dose Pingxiao capsule group/high-dose group(all P<0.050).There was a significant difference in nipple diameter between tamoxifen group and low-dose Pingxiao capsule group(P<0.050).(4)There were significant differences in serum levels of E_(2),GSH-Px,SOD,MDA and TNF-αamong groups(F=64.845,60.303,32.583,80.558,46.740,all P<0.050).Compared with the normal group,the levels of E_(2),MDA and TNF-αin model group were significantly increased(all P<0.050),while the levels of GSH-Px and SOD were significantly decreased(all P<0.050).There were significant differences in the levels of E_(2),GSH-Px,SOD,MDA and TNF-αbetween model group and tamoxifen group/medium-dose Pingxiao capsule group/high-dose group(all P<0.050);the levels of E_(2),GSH-Px,SOD and MDA all presented significant differences between tamoxifen group and medium-dose/high-dose Pingxiao capsule group(all P<0.050).(5)The viscera mass index of the uterus,thymus,spleen,liver and kidneys presented a significant difference among groups(F=3.502,1.696,13.672,2.995,4.465,all P<0.050).Compared with model group,the viscera mass index of the uterus,thymus and spleen in normal group,tamoxifen group,medium-dose Pingxiao capsule group and high-dose group all presented a significant difference(all P<0.050);there was a significant difference between tamoxifen group and low-dose/medium-dose/high-dose Pingxiao capsule group(all P>0.050).The results of HE staining showed that in medium-dose Pingxiao capsule group and high-dose group,the rats had significantly improved mammary tumor-like changes,hyperplasia and expansion of ducts,less acini and relieved lesions.Conclusion Pingxiao capsules are effective in prevention and treatment of DMBA-induced breast cancer in rats,which be due to its regulation on serum E_(2),GSH-Px,SOD,MDA and TNF-αlevels,as well as oxidative stress state of the body,thus improving the immune regulation.
作者
钟海林
蔡林
孙阳
陈贵娥
唐源
李宇华
董明芝
刘铁明
梅其炳
Zhong Hailin;Cai Lin;Sun Yang;Chen Guie;Tang Yuan;Li Yuhua;Dong Mingzhi;Liu Tieming;Mei Qibing(Department of Otolaryngology,First Naval Force Hospital of Southern Theater Command,Zhanjiang 524005,China;Department of Pharmacy,No.924 Hospital of People’s Liberation Army Joint Logistic Support Force,Guilin 541002,China;Department of Pharmacology,State Key Laboratory of Gastrointestinal Pharmacology of Traditional Chinese Medicine,Medical University of Air Forces,Xi’an 710032,China;Department of Pharmacy,First Naval Force Hospital of Southern Theater Command,Zhanjiang 524005,China;Xi’an C.P.Pharmaceutical Co.,Ltd.,Xi’an 710043,China)
出处
《中华乳腺病杂志（电子版）》
CAS
CSCD
2021年第2期82-89,共8页
Chinese Journal of Breast Disease(Electronic Edition)
关键词
胶囊
药物疗法
他莫昔芬
乳腺肿瘤
Capsules
Drug therapy
Tamoxifen
Breast neoplasms
