去甲斑蝥素对实验性过敏性结膜炎眼部炎症及Th1/Th2平衡的影响及机制

doi:10.3969/j.issn.1006-6233.2022.04.06

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Abstract Objective: To explore the regulating effect and mechanism of norcantharidin (NCTD) on ocular inflammation and Th1/Th2 balance in experimental allergic conjunctivitis (AC) rats. Methods: The SD rat AC model was established by the ovalbumin (OVA) method. The rats were randomly divided into control group, model group, NCTD low-dose group and NCTD high-dose group. Except for the control group, all other groups were induced with AC model, the NCTD low-dose and high-dose groups were given NCTD by gavage at 0. 05 mg·kg^-1·d^-1 and 0.1 mg·kg^-1·d^-1 respectively for 10 days; After the last sensitization of OVA, the rats were observed and scored for ocular signs, hematoxylin-eosin (HE) staining and periodate-Schiff (PAS) staining for histopathological changes in the cornea and conjunctiva, respectively, and enzyme-linked immunosorbent assay (ELISA) for the determination of cytokines IL-2, IL-4, IL-5, IL-10 and IFN-γ in the serum. Flow cytometry was performed to detect the ratio of Th1 and Th2 cells in spleen lymphocytes, real-time fluorescence PCR was performed to detect IL-4 and IFN-γ mRNA expression in conjunctival tissue, immunofluorescence staining was performed to detect VEGF expression in corneal tissue, and western blotting was performed to detect VEGF and VEGFR2 protein expression in conjunctival tissue. Results: After the rats were modeled, conjunctival hyperemia, redness, swelling, ocular fission, tearing, increased secretions and other AC pathological phenomena appeared. The inflammation score was higher than that of the control group (P<0.01), indicating that the AC animal model was successfully constructed. In the rats treated with the NCTD low-dose group and the NCTD high-dose group, the conjunctival congestion and redness were significantly relieved, tearing and secretion were reduced, the inflammation score decreased, the corneal epithelial cells were tightly arranged, neovascularization was reduced, and the numberthe of goblet cells in the conjunctiva increased, the serum levels of IL-2, IFN-γ increase, the levels of IL-4, IL-5 and IL-10 decrease, the ratio of Th1 cells and Th1/Th2 in the spleen both increased, and the ratio of Th2 cells decreaseed. The expression of IFN-γ mRNA in the conjunctival tissue was up-regulated, and the expression of IL-4 mRNA was down-regulated (all P＜0.01); at the same time, the positive expression rate of VEGF in corneal tissue decreased, and the expression of VEGF and VEGFR2 protein in conjunctival tissue were all down-regulated (all P<0.01). In addition, the effect of the high dose of NCTD was better than that of the low dose of NCTD (all P<0.01). Conclusion: Norcantharidin can alleviate the pathological process of experimental allergic conjunctivitis rats and improve Th1/Th2 cell immune imbalance by a mechanism that may be related to the inhibition of the VEGF pathway.

Key words： Allergic conjunctivitis Norcantharidin Th1/Th2 balance Vascular endothelial growth factor

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	ZHUANG Hairong
	WU Zidong
	CHEN Xuehong
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ZHUANG Hairong,WU Zidong,CHEN Xuehong, et al. A Preliminary Investigation on the Effect of Norcantharidin on Ocular Inflammation and Th1/Th2 Balance in Experimental Allergic Conjunctivitis and Its Mechanism[J]. HeBei Med, 2022, 28(4): 554-560.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.04.06 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I4/554

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