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江芝, 王磊, 刘学武, 张小冬, 彭冬冬, 陈相池, 王小青, 姜德建, 夏新华.基于Bax/Bcl-2信号通路探究钩藤提取物对实验兔复发性单纯疱疹病毒性角膜炎的作用[J].湖南中医药大学学报,2025,45(6):1014-1020[点击复制] |
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| 基于Bax/Bcl-2信号通路探究钩藤提取物对实验兔复发性单纯疱疹病毒性角膜炎的作用 |
| 江芝,王磊,刘学武,张小冬,彭冬冬,陈相池,王小青,姜德建,夏新华 |
| (湖南中医药大学药学院, 湖南 长沙 410208;新药药效与安全性评价湖南省重点实验室, 湖南普瑞玛药物研究中心有限公司, 湖南 长沙 410331;中南大学湘雅基础医学院, 湖南 长沙 410013) |
| 摘要: |
| 目的 基于Bcl-2 相关X蛋白（Bax）/B细胞淋巴瘤因子-2（Bcl-2）信号通路探究钩藤提取物对实验兔复发性单纯疱疹病毒性角膜炎（HSK）的作用。方法 选用普通级大耳白兔40只，随机分为正常对照组、模型对照组、阿昔洛韦组、钩藤水提取物组、钩藤醇提取物组，每组8只。除正常对照组外，其余各组均采用Ⅰ型单纯疱疹病毒感染眼部，并于感染后21 d（眼部感染症状恢复后），采用紫外线诱导复发性感染，以制备复发性HSK模型。模型对照组经眼滴入等量生理盐水，阿昔洛韦组每天灌胃阿昔洛韦，钩藤水提取物组和钩藤醇提取物组每天经眼滴入相应的钩藤提取物，连续干预14 d。分别于诱导复发后次日（给药前）、给药7 d、给药14 d进行角膜荧光染色评分；于给药前、给药14 d进行泪液病毒滴度检测；于给药14 d后进行角膜组织病理学检查，并采用Western blot检测角膜组织中Bax、Bcl-2、胱天蛋白酶-3（Caspase-3）的蛋白表达水平。结果 与正常对照组比较，模型对照组角膜荧光染色评分、泪液病毒滴度和角膜组织病理评分显著升高（P<0.01）；与模型对照组比较，给药14 d，钩藤水提取物组、钩藤醇提取物组和阿昔洛韦组角膜荧光染色评分和泪液病毒滴度均降低（P<0.05，P<0.01），阿昔洛韦组、钩藤醇提取物组的角膜组织病理评分显著降低（P<0.01）。与正常对照组比较，模型对照组角膜的Bax和Caspase-3蛋白表达均显著增加（P<0.01），Bcl-2蛋白表达显著减少（P<0.01）；与模型对照组比较，钩藤水提取物组、钩藤醇提取物组Caspase-3、Bax蛋白表达减少（P<0.05，P<0.01），Bcl-2蛋白表达增加（P<0.05）。与钩藤水提取物组比较，钩藤醇提取物组给药7 d和14 d的角膜荧光染色评分显著减小（P<0.01），泪液病毒滴度和角膜组织病理评分均显著降低（P<0.01）。结论 钩藤不同工艺提取物对复发性HSK具有显著治疗作用，其药理作用机制可能与其调节Bax/Bcl-2/Caspase-3凋亡信号通路，抑制病毒感染引起的角膜细胞凋亡有关，且钩藤醇提取物的药效作用更强。 |
| 关键词: Ⅰ型单纯疱疹病毒 单纯疱疹病毒性角膜炎 钩藤提取物 Bcl-2相关X蛋白 B细胞淋巴瘤因子-2 胱天蛋白酶-3 |
| DOI：10.3969/j.issn.1674-070X.2025.06.004 |
| 投稿时间：2025-03-16 |
| 基金项目:湖南省自然科学基金项目（2024JJ8140）；湖南省重点研发计划项目（2023DK2006）；长沙市“小荷”青年人才创新项目（〔2022〕056）。 |
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| Effects of Uncaria rhynchophylla extracts on recurrent herpes simplex keratitis in experimental rabbits via the Bax/Bcl-2 signaling pathway |
| JIANG Zhi, WANG Lei, LIU Xuewu, ZHANG Xiaodong, PENG Dongdong, CHEN Xiangchi, WANG Xiaoqing, JIANG Dejian, XIA Xinhua |
| (School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs & Hunan Prima Drug Research Center Co., Ltd., Changsha, Hunan 410331, China;Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, China) |
| Abstract: |
| Objective To investigate the effects of Uncaria rhynchophylla extracts on recurrent herpes simplex keratitis (HSK) in experimental rabbits based on the Bcl-2-associated X protein (Bax)/B-cell lymphoma factor 2 (Bcl-2) signaling pathway.Methods Forty common-grade big-eared white rabbits were randomly divided into normal control group, model control group, acyclovir group, aqueous extract of Uncaria rhynchophylla group, and alcoholic extract of Uncaria rhynchophylla group, with eight rabbits in each group. Except for the normal control group, all other groups were infected ocularly with herpes simplex virus type I (HSV-I). Twenty-one days after infection (when ocular infection symptoms had resolved), recurrent infection was induced using ultraviolet light to establish a recurrent HSK model. The model control group was administered an equal volume of normal saline via ocular drops, the acyclovir group received oral gavage of acyclovir daily, and The aqueous extract of Uncaria rhynchophylla group and the alcoholic extract of Uncaria rhynchophylla group were treated with the corresponding extracts via ocular drops daily for 14 consecutive days. Corneal fluorescence staining scores were assessed on the day after recurrence induction (before administration), on the 7th and 14th day of administration. Tear viral titers were measured before administration and on the 14th day of administration. Corneal histopathological examinations were conducted, and the protein expression levels of Bax, Bcl-2, and Caspase-3 in corneal tissue were checked by Western blot on the 14th day after administration.Results Compared with the normal control group, the model control group showed a significant increase in corneal fluorescein staining scores (P<0.01), tear viral titers, and corneal histopathological scores (P<0.01). After 14 days of administration, compared with the model control group, the alcoholic extract of Uncaria rhynchophylla group, and the acyclovir group all exhibited decreased corneal fluorescein staining scores and tear viral titers (P<0.05 or P<0.01). The acyclovir group and the alcoholic extract of Uncaria rhynchophylla group had significantly reduced corneal histopathological scores (P<0.01). Compared with the normal control group, the model control group showed significantly increased protein expression levels of Bax and Caspase-3 (P<0.01) and significantly decreased protein expression level of Bcl-2 (P<0.01) in the cornea. Compared with the model control group, the aqueous extract of Uncaria rhynchophylla group and the alcoholic extract of Uncaria rhynchophylla group had significantly reduced protein expression levels of Caspase-3 and Bax (P<0.05, P<0.01) and significantly increased protein expression level of Bcl-2 (P<0.05) in the cornea. Compared with the water extract group of Uncaria, the alcoholic extract group of Uncaria showed significantly lower corneal fluorescein staining scores at 7 and 14 days of administration (P<0.01). The alcoholic extract group of Uncaria had significantly lower tear virus titers and corneal tissue pathological scores (P<0.01).Conclusion Different extracts of Uncaria rhynchophylla have significant therapeutic effects on recurrent HSK, and the pharmacological mechanism may be related to their regulation of the Bax/Bcl-2/Caspase-3 apoptotic signaling pathway, thereby inhibiting virus-induced corneal cell apoptosis. Moreover, the alcoholic extract of Uncaria rhynchophylla demonstrates stronger pharmacological efficacy. |
| Key words: herpes simplex virus type I herpes simplex keratitis Uncaria rhynchophylla extracts Bcl-2-associated X protein B-cell lymphoma factor 2 Caspase-3 |
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