Cao Cheng, Yan Chunhong, Hu Zhiqiang, Zhou Shao
Department of Otorhinolaryngology, Yinzhou Hospital Affiliated to the Medical School of Ningbo University, Ningbo, Zhejiang 315000, P.R. China.
Department of Otorhinolaryngology, No. 113 Hospital of PLA, Ningbo, Zhejiang 315000, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6688-94. doi: 10.3892/mmr.2015.4237. Epub 2015 Aug 21.
Chronic rhinosinusitis is a condition with severe clinical symptoms and limited therapeutic solutions. It has been reported that vascular endothelial growth factor (VEGF) can promote nasal epithelial cell growth and result in hyperplasia of the sinuses. Therefore, the downregulation of VEGF may inhibit the process of hyperplasia. In the present study, small interfering RNA (siRNA) targeting VEGF was used to silence the expression of VEGF, and injectable chitosan based hydrogel, which is suitable for sinus injection and exhibits long‑term retention, was prepared as the siRNA carrier. Human bronchial epithelial cells were cultured directly on the hydrogel to observe the biological performance in vitro. Further in vivo effects were investigated by the injection of the hydrogel into the sinus cavity. Following the introduction of siRNA introducing, the expression of VEGF in the bronchial epithelial cells was significantly suppressed at mRNA and protein levels. The number of living cells on the gel was significantly decreased, thus resulting in the inhibition of proliferation. However, the cytoskeletal arrangement of the remaining cells were not affected substantially. The hydrogel was able to retain the siRNA for an extended duration, which enabled a sustained supply of siRNA. The in vivo sinus mucosa analysis revealed that the siRNA was able to collocate with cells and the mucosa thickness was substantially decreased. In conclusion, the results of the present study suggested that injectable chitosan based hydrogel, treated with siRNA targeting VEGF, may be used as a convenient therapeutic option for chronic rhinosinusitis.
慢性鼻窦炎是一种临床症状严重且治疗方案有限的疾病。据报道，血管内皮生长因子（VEGF）可促进鼻上皮细胞生长并导致鼻窦增生。因此，VEGF的下调可能会抑制增生过程。在本研究中，使用靶向VEGF的小干扰RNA（siRNA）来沉默VEGF的表达，并制备了适用于鼻窦注射且具有长期滞留性的可注射壳聚糖基水凝胶作为siRNA载体。将人支气管上皮细胞直接培养在水凝胶上以观察其体外生物学性能。通过将水凝胶注射到鼻窦腔中来研究其进一步的体内效应。在引入siRNA后，支气管上皮细胞中VEGF的表达在mRNA和蛋白质水平上均被显著抑制。凝胶上的活细胞数量显著减少，从而导致增殖受到抑制。然而，剩余细胞的细胞骨架排列基本未受影响。该水凝胶能够长时间保留siRNA，从而实现siRNA的持续供应。体内鼻窦黏膜分析显示，siRNA能够与细胞结合，且黏膜厚度显著降低。总之，本研究结果表明，经靶向VEGF的siRNA处理的可注射壳聚糖基水凝胶可作为慢性鼻窦炎的一种便捷治疗选择。
