TIMP-2基因转染在裸鼠胃癌中Ⅳ型胶原酶及Ⅳ型胶原改变的研究

Study of the changes of type Ⅳ collagen and type Ⅳ collagenase in TIMP2 gene transfected gastric carcinoma in nude mice

目的：探讨组织金属蛋白酶抑制剂（TIMP－2）基因体外转染胃癌SGC－7901细胞系后建立的裸鼠侵袭模型中的Ⅳ型胶原和Ⅳ型胶原酶改变的情况。方法：用TIMP－2基因体外转染的胃癌SGC－7901细胞系建立裸鼠肿瘤侵袭模型，并应用免疫组化对侵袭部位的组织Ⅳ型胶原和Ⅳ型胶原酶前体（MT－MMP）的改变作了研究。结果：正常肾脏组织Ⅳ型胶原酶反应阳性率与在种植肿瘤中阳性率两者差异显著（P＜0．01）。Ⅳ型胶原染色显示，肾小管及肾小球基底膜完整呈连续性线状分布，肿瘤部位的Ⅳ型胶原在基底膜处出现断裂和缺失，而肿瘤浸润部见Ⅳ型胶原酶表达异常丰富。结论：组织金属蛋白酶抑制剂TIMP－2基因转染参与肿瘤细胞分泌胶原酶的调控过程，抑制了Ⅳ型胶原的降解，是肿瘤侵袭、转移的重要负作用因子。

objective: To study the changes of type Ⅳ collagen and type Ⅳ collagenase in the tissue inhibitor of matrix metalloproteinase-2 gene (TIMP-2 ) in vitro transfected gastric carcinoma in nude mice.Methods: TIMP-2 gene was used to transfect in vitro SGC-7901 cell line of gastric carcinoma and this cell line was transferred to nude mice to establish the invasive model of gastric carcinoma. The changes of Ⅳ type Ⅳ collagen and the precursor of type Ⅳ collagenase (MT-MMP) were studied in the tissue of the invaded region with immunohistochemical assay. Results: The results showed that the positive rate of type Ⅳ collagenase (MT-MMP) was 36. 6% in normal kindey tissue and 70% in malignant lesions (P <0. 05). The intact patterns of type Ⅳ collagen was seen in normal groups while the disruptive and fragmentary patterns in malignants. Conclusions: The results suggest that TIMP-2 plays an important role in the destruction of type Ⅳ collagen and the promotion in the invasion and metastasis of gastric carcinoma.