文献类型：期刊文献

中文题名：基于NLRP3炎症小体探讨龙葵素膏治疗膝关节创伤性滑膜炎的机制及安全性

英文题名：Exploring Mechanism and Safety of Solanum Ointment in Treating Traumatic Synovitis of Knee Based on NLRP3 Inflammasome

作者：郝江峰[1];褚平铵[1];刘东[1];杨浩东[1];马纪龙[1];李宁[1];谢兴文[2];宋鹏[2]

第一作者：郝江峰

机构：[1]甘肃中医药大学中医临床学院,兰州730000;[2]甘肃中医药大学附属医院老年骨科,兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2025

卷号：54

期号：3

起止页码：320

中文期刊名：华中科技大学学报(医学版)

外文期刊名：Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金地区项目(No.82060873);兰州市人才创新创业项目(No.2021-RC-88);2023年陇原青年创新创业人才(团队)项目(No.甘组通字[2023]20号)。

语种：中文

中文关键词：皮肤刺激性试验;皮肤过敏性试验;膝关节创伤性滑膜炎;α-茄碱;NLRP3炎症小体

外文关键词：skin irritation test;skin allergy test;traumatic synovitis of the knee;α-solanine;NLRP3 inflammasome

摘要：目的评价龙葵素膏皮肤用药的安全性,并探讨龙葵素膏治疗膝关节创伤性滑膜炎模型兔的作用机制。方法将16只新西兰大白兔分为完整皮肤单次给药组、完整皮肤多次给药组、破损皮肤单次给药组、破损皮肤多次给药组,每组4只,通过脊柱两侧皮肤对照观察龙葵素膏的皮肤刺激性。将18只豚鼠分为空白组、龙葵素膏组、阳性药物组,每组6只,分别给予赋形剂、龙葵素膏和2,4-二硝基氯代苯,观察龙葵素膏的皮肤过敏性。然后选取30只新西兰大白兔,随机分为空白组、模型组、龙葵素膏低剂量组、龙葵素膏高剂量组和扶他林组,每组6只。除空白组外,均建立创伤性滑膜炎模型。外敷用药干预后观察各组兔膝关节周径和皮温变化;用苏木精-伊红(HE)染色法观察各组兔膝关节滑膜组织病理形态变化。用彩超观察膝关节关节积液和异常血流信号。采用ELISA法测定膝关节关节液中白介素1β(IL-1β)和白介素18(IL-18)的含量。Western blot法检测膝关节滑膜组织中NLRP3、pro-Caspase-1和cleaved-Caspase-1蛋白表达。结果皮肤刺激性试验结果显示完整皮肤单次给予龙葵素无刺激性,完整皮肤多次给予龙葵素观察的第1天有轻度刺激性,第3天消退;破损皮肤单次和多次给予龙葵素膏均存在中度刺激性。皮肤过敏性试验结果显示龙葵素膏组与空白组豚鼠均未出现过敏反应。与空白组相比,模型组兔膝关节周径和皮温明显升高(均P<0.01);滑膜增厚明显,有大量积液存在;滑膜细胞出现以浆细胞和淋巴细胞为主的炎性浸润,组织排列紊乱;膝关节关节液中IL-1β和IL-18的含量显著升高(均P<0.01);膝关节滑膜组织中NLRP3、pro-Caspase-1和cleaved-Caspase-1蛋白表达显著升高(均P<0.01)。与模型组比较,各药物治疗组兔膝关节周径和皮温均显著降低(均P<0.01);滑膜厚度、积液情况和滑膜炎性浸润均明显改善;膝关节关节液中IL-1β和IL-18的含量显著降低(均P<0.05);膝关节滑膜组织中NLRP3、pro-Caspase-1和cleaved-Caspase-1蛋白表达除龙葵素膏低剂量组无显著差异外(均P>0.05),龙葵素膏高剂量组和扶他林组均显著降低(均P<0.05)。结论龙葵素膏对完整皮肤存在轻度刺激性,对破损皮肤存在中度刺激性,龙葵素膏不适宜用于破损皮肤处,龙葵素膏对皮肤无致敏性。龙葵素膏能缓解膝关节创伤性滑膜炎的进展,其机制可能与调控NLRP3炎症小体有关。
Objective To evaluate the safety of Solanine ointment for skin application,and to investigate its mechanism of action in treating traumatic synovitis of the knee joint in a rabbit model.Methods Sixteen New Zealand white rabbits were divided into four groups(n=4 per group):intact skin single-dose group,intact skin multiple-dose group,damaged skin single-dose group,and damaged skin multiple-dose group.The skin irritation of Solanine ointment was assessed by comparing the skin on both sides of the spine in rabbits with intact and damaged skin.Eighteen guinea pigs were divided into three groups(n=6 per group):blank group,Solanine ointment group,and 2,4-dinitrochlorobenzene(DNCB)group.The blank group received the vehicle,the Solanine ointment group received Solanine ointment,and the DNCB group received DNCB.The skin allergic reactions were observed.Thirty New Zealand white rabbits were randomly divided into five groups(n=6 per group):blank group,model group,Solanine ointment low-dose group,Solanine ointment high-dose group,and Voltaren group.Except for the blank group,a traumatic synovitis model was established in the other groups.After topical application of the ointments,changes in knee joint circumference and skin temperature were measured.Pathological changes in knee joint synovial tissue were observed using hematoxylin-eosin(HE)staining.Joint effusion and abnormal blood flow signals were detected using color Doppler ultrasound.Levels of IL-1β and IL-18 in the synovial fluid were tested using ELISA.Protein expressions of NLRP3,pro-Caspase-l,and cleaved-Caspase-1 in the synovial tissue were determined using Western blotting.Results Skin irritation test showed that a single application of Solanine ointment on intact skin caused no irritation.Mild irritation was observed on the first day of multiple applications on intact skin,which subsided by the third day.Both single and multiple applications of Solanine ointment caused moderate irritation on damaged skin.Skin allergy test showed that no allergic reaction was observed in the guinea pigs of either the Solanine ointment group or the blank group.Compared with the blank group,the model group exhibited significantly increased knee joint circumference and skin temperature(both P<0.01),obvious synovial thickening with a large amount of effusion,inflammatory infiltration of synovial cells dominated by plasma cells and lymphocytes,disordered tissue arrangement,significantly elevated levels of IL-1β and IL-18 in the synovial fluid(all P<0.01),and significantly increased protein expression of NLRP3,pro-Caspase-1,and cleaved-Caspase-1 in the synovial tissue(all P<0.001).Compared with the model group,each drug treatment group showed significantly decreased knee joint circumference and skin temperature(all P<0.O1),improved synovial thickness,effusion,and inflammatory infiltration,significantly reduced levels of IL-1β and IL-18 in the synovial fluid(all P<.01).Except for the low-dose Solanine ointment group,high-dose Solanine ointment group and the Voltaren group showed significant reductions in protein expression of NLRP3,pro-Caspase-1,and cleaved-Caspase-1 in the synovial tissue(all P<0.05).Conclusion Solanine ointment exhibits mild irritation on intact skin and moderate irritation on damaged skin,therefore it is unsuitable for application on broken skin.There is no skin sensitization after application.Solanine ointment can alleviate the progression of traumatic synovitis of the knee joint,and its mechanism may be related to the regulation of the NLRP3 inflammasome.