欢迎访问《现代生物医学进展》编辑部！

作者	单位
闫丽晶	西安交通大学第二附属医院内分泌科陕西西安 710004
孙焕焕	西安交通大学第一附属医院消化内科陕西西安 710061
陈羽玲	西安交通大学第一附属医院消化内科陕西西安 710061
于晓慧	西安交通大学第一附属医院消化内科陕西西安 710061
张静茹	西安交通大学第一附属医院消化内科陕西西安 710061
李培杰	西安交通大学第一附属医院消化内科陕西西安 710061

摘要点击次数: 754

全文下载次数: 461

中文摘要:

摘要目的：研究青藤碱（SIN）对2型糖尿病（T2DM）合并肝癌（HCC）小鼠的治疗作用和可能机制。方法：将8周龄雄性BALB/c小鼠（20~25 g）分为Control组、T2DM+HCC组、SIN-L组、SIN-M组和SIN-H组。Control组小鼠正常饲养，其他组小鼠通过腹腔注射链脲佐菌素（STZ）联合肝实质内接种小鼠肝癌细胞（H22）建立T2DM+HCC小鼠模型。SIN-L组、SIN-M组和SIN-H组小鼠分别通过腹腔注射10、20和40 mg/kg/d的青藤碱，每天1次。Control组和T2DM+HCC组小鼠分别腹腔注射0.5 mL的生理盐水，各组小鼠均治疗21 d。末次给药24 h后，计算各组小鼠的肝脏指数并检测各组小鼠空腹血糖（FPG）、空腹血胰岛素（FINS）、血清总胆固醇（TC）、甘油三酯（TG）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）水平，肝脏组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）和丙二醛（MDA）水平。通过苏木精和伊红（HE）染色观察肝脏形态，Western blot检测肝脏组织中BCL2、BAX、P53、信号转导和转录激活因子3（STAT3）、细胞因子信号抑制因子3（SOCS3）和固醇调节元件结合蛋白-1（SREBP-1）的蛋白表达。结果：T2DM+HCC组、SIN-L组、SIN-M组和SIN-H组小鼠的中位生存期依次为25、32、35和41 d，组间比较差异有统计学意义（P<0.001），随着青藤碱浓度的升高，小鼠的中位生存期延长。与T2DM+HCC组比较，SIN-L组、SIN-M组和SIN-H组小鼠的血清FPG、FINS、TC、TG、ALT、AST和LDH水平降低，肝细胞排列基本规则，水肿、空泡样变性和炎性细胞浸润等病变明显减轻，肝脏指数降低，肝脏SOD、CAT和GSH-PX水平升高，肝脏MDA水平降低，肝脏BCL2蛋白表达水平降低，肝脏BAX和P53蛋白表达升高（P<0.05）。与T2DM+HCC组比较，SIN-L组、SIN-M组和SIN-H组小鼠肝脏组织STAT3 Tyr705磷酸化、SOCS3和SREBP-1蛋白表达降低（P<0.05）。结论：青藤碱可有效延长2型糖尿病合并肝癌小鼠的生存时间，稳定血糖和血脂水平，改善肝功能，并抑制癌细胞生长，其机制可能与抑制STAT3信号通路有关。

英文摘要:

ABSTRACT Objective: To investigate the therapeutic effect and possible mechanism of sinomenine (SIN) on type 2 diabetic (T2DM) mice with liver cancer (HCC). Methods: Eight-week-old male BALB/c mice (20-25 g) were divided into Control, T2DM+HCC, SIN-L, SIN-M and SIN-H group. Mice in the Control group were fed normally, and mice in other groups were injected intraperitoneally with streptozotocin (STZ) and inoculated with hepatocellular carcinoma cells (H22) in liver parenchyma to establish T2DM combined with HCC mice model. Mice in the SIN-L, SIN-M and SIN-H group were intraperitoneally injected with 10, 20 and 40 mg/kg/d of sinomenine, respectively. Mice in the Control group and T2DM+HCC group were intraperitoneally injected with 0.5 mL of normal saline respectively. All the mice were treated for 21 days. 24 hours after the last administration, the liver index was calculated and fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglyceride (TG)], alanine aminotransferase (ALT), aspartate aminotransferase(AST) and lactate dehydrogenase(LDH), liver superoxide dismutase(SOD), catalase (CAT), Glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels were detected. Liver morphology was observed by hematoxylin and eosin (HE) staining. The protein expression of BCL2, BAX, P53, signal transducer and activator of transcription 3 (STAT3), cytokine signal inhibitor 3(SOCS3) and sterol regulatory element binding protein-1(SREBP-1) in liver tissue were detected by Western blot. Results: The median survival time of T2DM+HCC group, SIN-L group, SIN-M group and SIN-H group was 25, 32, 35 and 41 days respectively(P<0.001), the median survival time of mice extended with the increase of sinomenine concentration. Compared with T2DM+HCC group, the levels of FPG, FINS, TC and TG in SIN-L, SIN-M and SIN-H group decreased, serum ALT, AST and LDH levels decreased, the basic rules of hepatic cell arrangement, edema, vacuolar degeneration, inflammatory cell infiltration and other lesions were significantly reduced, liver index decreased, liver SOD, CAT and GSH-PX levels increased, liver MDA level decreased, liver BCL2 protein expression decreased, liver BAX and P53 protein expression increased(P<0.05). Compared with T2DM+HCC group, the expression of p-STAT3 (Tyr705), SOCS3 and SREBP-1 protein in liver of SIN-L, SIN-M and SIN-H group decreased in a dose-dependent manner(P<0.05). Conclusion: Sinomenine can effectively prolong the survival time of type 2 diabetic mice with liver cancer, improve the blood glucose and lipid levels as well as the live function, and inhibit the growth of cancer cells, which may be related to the inhibition of STAT3 signaling pathway.

查看全文查看/发表评论下载PDF阅读器

关闭