大鼠颌下腺腺病毒介导荧光素酶基因转导及组织学变化

目的 观察大白鼠颌下腺腺病毒介导的荧光素酶基因转导及其组织学变化。方法 将40只Wistar大鼠随机分为5组，经颌下腺导管转导腺病毒介导荧光素酶基因重组体即AdCMVLuc,3d及1、2、4、8周后观察其基因表达及病理变化。结果 颌下腺转基因表达3d时最高，以后逐渐下降，至4周、8周时仍可测到表达。组织病理学变化：3d-1周时可见腺泡受挤压、腺导管扩张；2周时部分腺泡轻度萎缩，腺泡间距离加大；小叶内及小叶间导管周围淋巴细胞呈灶状浸润；4周时可见有腺泡及腺泡腔结构变清晰；8周时腺泡、导管基本恢复正常，炎症不明显。超微结构变化；注入基因后3d，腺泡和导管细胞内可见大量粗面内质网，粘液腺泡中粘液滴增多，融合成片；1周后，导管腔的微绒毛突起减少，胞质内可见线粒体显著增多；2周及4周，腺泡腔可见少量的微绒毛突起及细丝网状物，粘液腺泡中可见粘液滴。基底部可见粗面内质网，基底膜增厚。结论 本研究报道了腺病毒介导的大鼠颌下腺基因转导后的超微结构变化，提示腺体蛋白合成体系功能活跃，大鼠涎腺基因转导能产生生物活性蛋白，腺体有明显炎症反应。

Gene expression and pathological changes of rat submandibular glands after adenovirus-mediated gene transfer

OBJECTIVE: To investigate luciferase gene expression and pathological changes of submandibular glands (SMG) of rats after adenovirus-mediated gene transfer. METHODS: Adenovirus-mediated luciferase gene (AdCMVLuc, 10(8) pfu in 50 microl) was injected in to SMG of forty wistar rats. The SMGs were harvested for gene expression measurement and pathological study after 3 days, 1,2,4 and 8 weeks. RESULTS: Peak expression was observed in three days following administration of the vector however, gene expression in submandibular glands decreased rapidly. the pathological changes induced by retrograde injection of AdCMVLuc included: after 3 days to one week, compression of acini, dilation of terminal ducts; after two weeks, slight atrophy of a part of acini, increase of iteracinar distance and focal lymphocyte infiltration in lobules and interlobular ducts; after 4 weeks, recovery evidence was found in acini; after 8 weeks, normal acini and ducts were found. The ultrastructural changes included: 3 days, much more rough endoplasmic reticulum was found both in acini and duct epithelial cell; a lot of mucus drops were found in acini; after 1 week, microvillus decreased in duct epithelial cells, mitochondria increased significantly in acini; intercellular space was enlarged. CONCLUSIONS: Adenovirus-mediated gene transfer can produce biological proteins and induce marked inflammatory changes in rat SMG. The ultrastructural changes suggest high protein synthesis activity in the acinar cells after gene transfer.