鼻渊舒口服液影响分子伴侣HSP70及辅助因子CHIP干预CRS模型鼻窦黏膜炎症的研究

Effects of Biyuanshu on Molecular Chaperone HSP70 and Cofactor CHIP Expression of Nasal Sinuses Mucosa Epithelial in Mice Chronic Rhinosinusitis Model

目的:观察慢性鼻-鼻窦炎(CRS)时,鼻渊舒口服液对鼻窦黏膜上皮分子伴侣HSP70及其辅助因子CHIP的影响,从分子伴侣系统角度探索鼻渊舒治疗CRS的机制。方法:140只雄性C57小鼠,每组20只,随机分为正常对照组、假手术组、模型组、克拉霉素阳性对照组及鼻渊舒口服液低、中、高剂量组,建立CRS模型,以相应药物治疗14 d。HE染色观察鼻窦黏膜组织病理学变化,实时定量PCR鼻窦黏膜HSP70、CHIP mRNA表达,Western Blot法检测鼻窦黏膜HSP70、CHIP蛋白表达及IKK活性。结果:模型组鼻窦黏膜上皮大片坏死脱落,慢性炎细胞浸润明显;HSP70及CHIP的mRNA及蛋白表达较正常对照组及假手术组显著降低(P<0.05或P<0.01),p-IKKα/β表达较正常对照组及假手术组显著增高(P<0.01)。与模型组比较,鼻渊舒中、高剂量组鼻窦黏膜上皮修复较好,排列较为整齐,慢性炎细胞浸润明显减轻;CHIP及HSP70 mRNA及蛋白表达显著增高(P<0.01),p-IKKα/β表达显著降低(P<0.01)。结论:鼻渊舒能促进CRS小鼠鼻窦黏膜上皮修复,其机制可能与其增加鼻窦黏膜上皮分子伴侣HSP70及其辅助分子CHIP表达,增强细胞内蛋白质损伤保护机制,抑制IKK活性及其下游的NF-κB炎症通路有关。

Objective： To investigate effects of Biyuanshu（ BYS） on molecular chaperone HSP70 and carboxyl terminus of HSC70 /HSP70-interacting protein（ CHIP） expression of nasal sinuses mucosa epithele in mice Chronic rhinosinusitis（ CRS） model,and to explore the BYS intervention mechanism from the point of molecular chaperone system. Methods： 140 C57 male mice were randomly divided into normal group,sham operation group,model group,western medicine group,BYS low-dosage group,BYS medium-dosage group,BYS high-dosage group,with 20 mice in each group,and CRS model was established. With corresponding drug treatment for 14 days. Nasal sinuses mucosa tissue was collected to observe pathological alterations after HE dyeing,and HSP70 and its cofactor CHIP mRNA expression in nasal sinuses mucosa epithele were detected by real-time PCR,and the protein expression and IKK activity were detected by Western blotting. Results： Model group appeared large necrotic and falling-off areas,apparently accompanied with chronic inflammatory cell infiltration. Nasal sinuses mucosa epithelial chaperon HSP70 and its cofactor CHIP expressions were much lower in CRS group than normal group and slam operation group（ P 〈0. 05 or P 〈0. 01）,p-IKKα / β expression in model group was obviously higher than normal group and slam operation group（ P 〈0. 01）. Compared to model group,BYS medium-dosage and high-dosage groups presented well-repaired epithele in alignment,with fewer chronic inflammatory cell infiltration. Furthermore,expression of chaperon HSP70 and its cofactor CHIP in nasal sinuses mucosa epithelium were much higher than model group（ P 〈0. 01）,but the p-IKKα / β expression was lower（ P 〈0. 01）. Conclusion： BYS can upregulate chaperon HSP70 and its cofactor CHIP to enhance intracellular protection from inflammatory protein injury mice,and reduce IKK activity to intervene on downstream NF-κB signaling pathway. BYS can be in favor of nasal sinuses mucosa epithelial repairmen.