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血管生成素及血管内皮生长因子在结直肠疾病模型中的表达

Angiopoietin and vascular endothelial growth factor expression in colorectal disease models.

作者信息

Liu Wei-Xin, Gu Shou-Zhi, Zhang Shen, Ren Yi, Sang Li-Xuan, Dai Cong

机构信息

Wei-Xin Liu, Shen Zhang, Yi Ren, Li-Xuan Sang, Cong Dai, Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.

出版信息

World J Gastroenterol. 2015 Mar 7;21(9):2645-50. doi: 10.3748/wjg.v21.i9.2645.

DOI:10.3748/wjg.v21.i9.2645
PMID:25759532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4351214/
Abstract

AIM

To investigate angiopoietin (Ang) and vascular endothelial growth factor (VEGF) expression in rats with ulcerative colitis (UC) and colorectal cancer (CRC).

METHODS

Dysplasia and cancer were investigated in rats that received three cycles of 3.5% dextran sulfate sodium (DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine (DMH) (CRC group). Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline (UC group). Rats without DSS or DMH treatment served as controls. Expression of the tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2 and its ligands, Ang-1 and Ang-2, as well as VEGF were evaluated in the colorectum by Western blotting.

RESULTS

Compared with rats in the control group, rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea, rectal bleeding, wasting, and loss of body weight (P < 0.05). In addition, the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats (8.29 ± 0.21 and 8.31 ± 0.86, respectively, vs 12.34 ± 0.12 cm; P < 0.05). Furthermore, rats in the CRC group, but not in the UC or control groups, developed multiple tumors in the colorectal region. Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1, Ang-2, Tie-2, and VEGF in the colorectum compared to rats in the control group.

CONCLUSION

Increased expression of Ang-1, Ang-2, Tie-2, and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.

摘要

目的

研究血管生成素(Ang)和血管内皮生长因子(VEGF)在溃疡性结肠炎(UC)和结直肠癌(CRC)大鼠中的表达情况。

方法

对经腹腔注射20 mg/kg 1,2 - 二甲基肼(DMH)预处理后,饮用含3.5%硫酸葡聚糖钠(DSS)的水7天,随后饮用蒸馏水14天,共三个周期的大鼠进行发育异常和癌症情况的研究(CRC组)。对经腹腔注射生理盐水预处理后,饮用含3.5% DSS的水7天,随后饮用蒸馏水14天,共三个周期的大鼠进行结肠炎情况的研究(UC组)。未接受DSS或DMH处理的大鼠作为对照。通过蛋白质印迹法评估结肠直肠中具有免疫球蛋白样和表皮生长因子样结构域的酪氨酸激酶(Tie)-2及其配体Ang-1和Ang-2以及VEGF的表达。

结果

与对照组大鼠相比,CRC组和UC组大鼠出现了急性结肠炎症状,包括腹泻、直肠出血、消瘦和体重减轻(P < 0.05)。此外,CRC组和UC组大鼠的结肠直肠平均长度明显短于对照组大鼠(分别为8.29 ± 0.21和8.31 ± 0.86 cm,对照组为12.34 ± 0.12 cm;P < 0.05)。此外,CRC组大鼠在结肠直肠区域出现了多个肿瘤,而UC组和对照组大鼠未出现。蛋白质印迹分析显示,与对照组大鼠相比, CRC组和UC组大鼠结肠直肠中Ang-1、Ang-2、Tie-2和VEGF的蛋白质水平明显升高。

结论

溃疡性结肠炎衍生的结直肠癌中Ang-1、Ang-2、Tie-2和VEGF表达增加可能导致大鼠慢性结肠炎和病理性血管生成。

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