Intragland Shh gene delivery mitigated irradiation-induced hyposalivation in a miniature pig model.
Intragland Shh gene delivery mitigated irradiation-induced hyposalivation in a miniature pig model.
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在小型猪模型中，腺内 Shh 基因传递减轻了辐射引起的唾液分泌不足。
作者：
Hu L;Zhu Z;Hai B;Chang S;Ma L;Xu Y;Li X;Feng X;Wu X;Zhao Q;Qin L;Wang J;Zhang C;Liu F;Wang S
不可逆的唾液腺功能减退在接受放疗的头颈癌幸存者中很常见，目前的治疗只能暂时缓解。我们最近在小鼠模型中发现，照射后短暂激活Hedgehog通路可通过保护唾液腺干/祖细胞、副交感神经支配和微血管来恢复唾液腺功能。由于啮齿类动物和人类唾液腺之间存在巨大差异，为了研究这种方法的转化潜力，我们在辐照诱导的低涎化微型猪模型中评估了Shh基因转移的影响。方法：用20格雷单剂量照射猪右腮腺。在照射后4周或16周，通过无创逆行导管注入相应的腺病毒载体，将Shh和对照GFP基因传递到受照射的腮腺中。每两周采集一次腮腺唾液。照射后5周或20周收集腮腺进行组织学、Western blot和qRT-PCR检测。结果：在照射后4周传递Shh基因可显著改善受刺激的唾液分泌和局部血液供应，持续20周，保留小鼠模型中产生唾液的腺泡细胞、副交感神经支配和微血管，并激活受照射腺体的自噬和抑制纤维生成。结论：这些数据提示了瞬时激活Hedgehog通路在保护照射后唾液功能中的翻译潜力。
Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found recently in mouse models that transient activation of Hedgehog pathway following irradiation rescued salivary gland function by preserving salivary stem/progenitor cells, parasympathetic innervation and microvessels. Due to huge differences between salivary glands of rodents and humans, to examine the translational potential of this approach, we evaluated effects of Shh gene transfer in a miniature pig model of irradiation-induced hyposalivation. Methods: The right parotid of each pig was irradiated with a single dose of 20 Gray. Shh and control GFP genes were delivered into irradiated parotid glands by noninvasive retrograde ductal instillation of corresponding adenoviral vectors 4 or 16 weeks after irradiation. Parotid saliva was collected every two weeks. Parotid glands were collected 5 or 20 weeks after irradiation for histology, Western blot and qRT-PCR assays. Results: Shh gene delivery 4 weeks after irradiation significantly improved stimulated saliva secretion and local blood supply up to 20 weeks, preserved saliva-producing acinar cells, parasympathetic innervation and microvessels as found in mouse models, and also activated autophagy and inhibited fibrogenesis in irradiated glands. Conclusion: These data indicate the translational potential of transient activation of Hedgehog pathway to preserve salivary function following irradiation.
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影响因子：
4.4
作者：
Gluck C;Min S;Oyelakin A;Smalley K;Sinha S;Romano RA
通讯作者：
Romano RA
影响因子：
5.1
作者：
Guo, L.;Gao, R.;Wang, S.
通讯作者：
Wang, S.
DOI：
10.1016/j.ijrobp.2003.09.021
发表时间：
2004-04-01
影响因子：
7
作者：
Roesink, JM;Moerland, MA;Terhaard, CHJ
通讯作者：
Terhaard, CHJ
影响因子：
4
作者：
Hai, Bo;Yang, Zhenhua;Liu, Fei
通讯作者：
Liu, Fei
影响因子：
2.4
作者：
Amano O;Mizobe K;Bando Y;Sakiyama K
通讯作者：
Sakiyama K