| 摘要: |
| 目的 探究加味旋覆代赭汤对食管癌前病变大鼠Caspase-3/Bcl-2/Bax信号通路的调控作用机制。方法:将48只雄性SD大鼠随机分为4组，空白组、模型组、中药组、西药组，每组各12只。除空白组外均采用复合造模法制作食管癌前病变大鼠模型，造模成功后，分别进行药物灌胃干预，空白组、模型组用生理盐水灌胃，中药组和西药组分别给予加味旋覆代赭汤、西药(雷贝拉唑+莫沙必利)灌胃，给药8周取材。利用光学显微镜观察食管上皮组织的形态学变化；分别应用蛋白质印迹法(Western-blot)及聚合酶链式反应(PCR)检测食管上皮组织Caspase-3、Bcl-2及Bax的表达水平。结果:与空白组比较，模型组大鼠食管上皮病理积分升高(P<0.01)；与模型组比较，中药组、西药组大鼠食管上皮病理积分均降低(P<0.01)。PCR及Western-blot检测结果显示，与空白组比较，模型组大鼠Caspase-3、Bax mRNA、蛋白表达均降低(P<0.01)；与模型组比较，中药、西药组大鼠Caspase-3、Bax mRNA、蛋白表达均增高(P<0.05)。与空白组比较，模型组大鼠食管组织中Bcl-2 mRNA及蛋白表达水平均升高(P<0.05)；与模型组比较，中药组和西药组Bcl-2 mRNA及蛋白表达水平均降低(P<0.05)。结论:加味旋覆代赭汤可能通过下调Bcl-2/Bax比值，增加线粒体外膜通透性，释放凋亡因子，激活Caspase-3，使病变组织发生凋亡，扭转食管上皮异型增生，从而起到治疗食管癌前病变的作用。 |
| 关键词: 食管癌前病变 加味旋覆代赭汤 Caspase-3 Bcl-2 Bax 细胞凋亡 |
| DOI：10.3969/j.issn.1007-6948.2024.02.022 |
| 投稿时间：2023-06-01 |
| 基金项目:天津市自然科学基金(S21DYZD3085) |
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| Exploring the mechanism of Jiawei Xuanfu Daizhe decoction in treating esophageal precancerous lesions based on the Caspase3/Bcl-2/Bax signaling pathway |
| TIAN Jing-jing，YUAN Hong-xia，ZHANG Yue-lin |
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| Abstract: |
| Objective To explore the regulatory mechanism of Jiawei Xuanfu Daizhe decoction on the Caspase-3/Bcl-2/Bax signaling pathway in rats with esophageal precancerous lesions. Methods Forty-eight male SD rats were randomly divided into four groups: Blank group, Model group, Chinese Medicine group, and Western Medicine group, with 12 rats in each group. Except for the Blank group, esophageal precancerous lesion rat models were created using a compound modeling method. After successful modeling, drug intervention was performed by gavage. The Blank and Model groups were given normal saline, while the Chinese Medicine and Western Medicine groups were given Jiawei Xuanfu Daizhe decoction and Western Medicine (rabeprazole+mosapride), respectively. Tissues were collected after 8 weeks of treatment. Optical microscope was used to observe the morphological changes in esophageal epithelial tissues. Protein imprinting (Western blot) and polymerase chain reaction (PCR) were used to detect the expression levels of Caspase-3, Bcl-2, and Bax in esophageal epithelial tissues. Results Compared with the Blank group, the pathological scores of esophageal epithelium in the Model group increased significantly (P<0.01). Compared with the Model group, the pathological scores decreased significantly in the Chinese Medicine and Western Medicine groups (P<0.01). PCR and Western blot results showed that compared with the Blank group, the expression of Caspase-3 and Bax mRNA and protein in the Model group rats decreased significantly (P<0.01). Compared with the Model group, the expression of Caspase-3 and Bax mRNA and protein increased significantly in the Chinese Medicine and Western Medicine groups (P<0.05). Compared with the Blank group, the expression levels of Bcl-2 mRNA and protein in the esophageal tissues of the Model group rats increased (P<0.05). Compared with the Model group, the expression levels of Bcl-2 mRNA and protein decreased in the Chinese Medicine and Western Medicine groups (P<0.05). Conclusion Jiawei Xuanfu Daizhe decoction may play a role in treating esophageal precancerous lesions by down-regulating the Bcl-2/Bax ratio, increasing mitochondrial membrane permeability, releasing apoptotic factors, activating Caspase-3, inducing apoptosis in the lesion tissue, and reversing esophageal epithelial dysplasia. |
| Key words: Esophageal precancerous lesions Jiawei Xuanfu Daizhe decoction Caspase-3 Bcl-2 Bax apoptosis |
