[1]李方凯,谷新怡,朱跃兰,等.活血解毒润燥方干预干燥综合征小鼠颌下腺细胞凋亡促进因子Smac表达的机制研究[J].陕西中医,2023,(6):693-698.[doi:DOI:10.3969/j.issn.1000-7369.2023.06.003]
　LI Fangkai,GU Xinyi,ZHU Yuelan,et al.Research on the mechanism of apoptosis promoting factor Smac expression in submandibular gland cells of Sjogren's syndrome mice intervened by Huoxue Jiedu Runzao prescription[J].,2023,(6):693-698.[doi:DOI:10.3969/j.issn.1000-7369.2023.06.003]
点击复制

活血解毒润燥方干预干燥综合征小鼠颌下腺细胞凋亡促进因子Smac表达的机制研究
分享到：

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2023年6期
页码:
693-698
栏目:
基础研究
出版日期:
2023-06-05

文章信息/Info

Title:
Research on the mechanism of apoptosis promoting factor Smac expression in submandibular gland cells of Sjogren's syndrome mice intervened by Huoxue Jiedu Runzao prescription
作者:
李方凯1; 谷新怡2; 朱跃兰1; 侯秀娟1; 曹云松1
(1.北京中医药大学东方医院,北京100078; 2.北京中医药大学东直门医院通州院区,北京101121)
Author(s):
LI Fangkai; GU Xinyi; ZHU Yuelan; HOU Xiujuan; CAO Yunsong
(Dongfang Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100078,China)
关键词:
干燥综合征;  活血解毒润燥方;  白芍总苷胶囊;  颌下腺;  细胞凋亡;  细胞凋亡促进因子Smac
Keywords:
Sjogren's syndrome;  Huoxue Jiedu Runzao prescription;  Total glucosides of paeony capsule;  Submandibular gland;  Apoptosis;  Apoptosis promoting factor Smac
分类号:
R 593.2
DOI:
DOI:10.3969/j.issn.1000-7369.2023.06.003
文献标志码:
A
摘要:
目的:将干燥综合征(SS)模型小鼠颌下腺细胞凋亡促进因子Smac的表达作为靶点,探究活血解毒润燥方对SS模型小鼠颌下腺组织形态、腺体功能、细胞凋亡的影响及其干预机制。方法:实验选取雌性BALB/c57小鼠为正常对照组,自发性雌性非肥胖型糖尿病(NOD/Ltj)小鼠为SS模型并随机分为模型组、白芍总苷胶囊组和活血解毒润燥方低、中、高剂量组,每组各15只。各组小鼠给药量按照人与动物体表面积比计算等效剂量,正常对照组、模型组小鼠灌胃10 ml/kg蒸馏水,白芍总苷胶囊组(0.234 g/kg)和活血解毒润燥方低剂量组(15.6 g/kg)、中剂量组(31.2 g/kg)、高剂量组(62.4 g/kg)分别灌胃给药,每日1次。药物干预8周后,无菌分离颌下腺,观察各组小鼠颌下腺形态、功能的改变,并分别应用免疫组化法(IHC)、蛋白免疫印迹法(Western blot)、逆转录聚合酶链式反应(RT-PCR)测定细胞凋亡促进因子Smac的表达。结果:与正常对照组比较,模型组唾液流量及颌下腺指数均显著降低(P<0.01),颌下腺组织病理学评分显著升高(P<0.01),IHC和Western blot检测Smac表达明显升高(P<0.05),RT-PCR检测Smac表达显著升高(P<0.01)。治疗结束后,与模型组比较,活血解毒润燥方各剂量组和白芍总苷胶囊组唾液流量及颌下腺指数均显著升高(P<0.01),颌下腺组织病理学评分显著降低(P<0.01)。运用IHC和Western blot检测活血解毒润燥方高剂量组和白芍总苷胶囊组Smac表达明显降低(P<0.05),运用RT-PCR检测活血解毒润燥方高剂量组与白芍总苷胶囊组Smac表达显著降低(P<0.01)。结论:活血解毒润燥方可以改善SS模型鼠颌下腺腺泡的分泌功能,提高其颌下腺指数,增加SS模型鼠的唾液分泌量; 其作用机制与下调SS模型鼠颌下腺细胞凋亡、促进因子Smac的表达水平有关。
Abstract:
Objective:To investigate the effect of Huoxue Jiedu Runzao prescription on the tissue morphology,glandular function and cell apoptosis of submandibular gland in Sjogren's syndrome(SS)model mice and its intervention mechanism,using the expression of apoptosis promoting factor Smac as the target.Methods:Female BALB/c57 mice were selected as normal control group,and spontaneous female non-obese diabetes mellitus(NOD/Ltj)mice were selected as SS model.The mice were randomly divided into model group,total glucosides of paeony capsule group(TGPC)and Huoxue Jiedu Runzao prescription low-dose,medium-dose and high-dose groups,with 15 mice in each group.The dosage of mice in each group was calculated according to the ratio of body surface area between human and animal.Mice in normal control group and model group were intragastric with 10 ml/kg distilled water.Total glucosides of paeony capsule group(0.234 g/kg),low dose group(15.6 g/kg),medium dose group(31.2 g/kg)and high dose group(62.4 g/kg)of Huoxue Jiedu Runzao prescription were administrated by intragastric administration,once a day.After 8 weeks of drug intervention,submandible gland was separated aseptically,and the morphological and functional changes of submandible gland in each group were observed.The expression of apoptosis promoting factor Smac was detected by IHC,Western blot and RT-PCR,respectively.Results:Compared with the normal control group,the saliva flow and submandibular gland index in the model group were significantly decreased(P<0.01),histopathological scores of submandibular gland were significantly increased(P<0.01),the expression of Smac was significantly increased by IHC and Western blot(P<0.05),the expression of Smac was significantly increased by RT-PCR(P<0.01).After treatment,compared with model group,saliva flow and submandibular gland index of Huoxue Jiedu Runzao prescription and total glucosides of paeony capsule group were significantly increased(P<0.01),the submandibular gland histopathological score was significantly decreased(P<0.01).The expression of Smac in Huoxue Jiedu Runzao prescription high-dose group and total glucosides of paeony capsule group was significantly decreased by IHC and Western blot analysis(P<0.05),the expression of Smac in Huoxue Jiedu Runzao prescription high-dose group and total glucosides of paeony capsule group was significantly decreased by RT-PCR(P<0.01).Conclusion:Huoxue Jiedu Runzao prescription can improve the secretory function of the submandibular gland acinus,increase the submandibular gland index and increase the saliva secretion of SS model mice.Its mechanism of action is related to down-regulating the expression level of Smac in SS model mice submandibular gland cell apoptosis promoter.

参考文献/References:

[1] Bjordal O,Norheimk B,Rodahl E,et al.Primary sjogren's syndrome and the eye[J].Surv Ophthalmol,2020,65(2):119-132.
[2] 侯佳奇,薛 鸾.原发性干燥综合征发病机制概述[J].现代免疫学,2019,39(1):60-65.
[3] An W,Lai H,Zhang Y,et al.Apoptotic pathway as the therapeutic target for anticancer traditional Chinese medicines[J].Front Pharmacol,2019,10:758-783.
[4] 黄智超,李国峰,郎一帆,等.中药诱导肺癌细胞凋亡机制的研究进展[J].中国实验方剂学杂志,2021,27(23):226-236.
[5] 朱跃兰,侯秀娟,韦 尼.干燥综合征从燥毒瘀辨证论治[J].北京中医药大学学报,2009,32(6):416-418.
[6] 李方凯,谷新怡,崔民英,等.活血解毒方对干燥综合征小鼠颌下腺AQP5表达的影响[J].西部中医药,2016,29(9):19-22.
[7] 毛晓娟.干燥综合征患者外周血中Treg和Th17细胞绝对数量与肠道微生物菌落特征的相关性研究[D].太原:山西医科大学,2020.
[8] 徐叔云.药理实验方法学[M].北京:人民卫生出版社,1982:129-131.
[9] Sauler M,Bazan IS,Lee PJ.Cell death in the lung:The apoptosis-necroptosis axis[J].Annu Rev Physiol,2019,81(1):375-402.
[10] 杨 洁,范引科,宋延平,等.扶脾化瘤饮诱导胃癌小鼠细胞凋亡和相关凋亡基因表达的机制研究[J].陕西中医,2019,40(5):550-552,590.
[11] 傅 娟,刘媛媛,李 霞.小白菊内酯对小儿血管瘤内皮细胞凋亡的影响实验研究[J].陕西医学杂志,2021,50(5):525-528.
[12] 纪 涛,任建政,李正华,等.小白菊内酯对骨肉瘤细胞凋亡与凋亡相关蛋白的影响及作用机制研究[J].陕西医学杂志,2022,51(2):151-154,163.
[13] 魏 娟,张全安.第二线粒体源性胱氨酸酶激活因子及其类似物与肿瘤的相关性研究进展[J].安徽医药,2016,20(10):1823-1826.
[14] Kumar S,Fairmichael C,Longley DB,et al.The multiple roles of the IAP super-family in cancer[J].Pharmacol Ther,2020,214:107610-107665.
[15] Mohamed MS,Bishr MK,Almutairi FM,et al.Inhibitors of apoptosis:Clinical implications in cancer[J].Apoptosis,2017,22(12):1487-1509.
[16] Abbas R,Larisch S.Targeting XIAP for promoting cancer cell death-the story of ARTS and SMAC[J].Cells,2020,9(3):663-678.
[17] Vasilikos L,Spilgies LM,Knop J,et al.Regulating the balance between necroptosis,apoptosis and inflammation by inhibitors of apoptosis proteins[J].Immunol Cell Biol,2017,95(2):160-165.
[18] 胡文秀,冯 波,陆定其,等.浅议从湿论治干燥综合征[J].浙江中医杂志,2021,56(1):4-6.
[19] 李向阳,许甜甜,沈炳香,等.干燥综合征的中医药治疗规律浅析[J].江西中医药大学学报,2021,33(3):44-47.
[20] 周雯怡,苏 励.苏励教授治疗干燥综合征经验撷要[J].陕西中医,2022,43(5):640-643.

相似文献/References:

[1]周雯怡,苏 励.苏励教授治疗干燥综合征经验撷要[J].陕西中医,2022,(5):640.[doi:DOI:10.3969/j.issn.1000-7369.2022.05.023]
　ZHOU Wenyi,SU Li.SU Li's experience in the treatment of Sjogren's syndrome[J].,2022,(6):640.[doi:DOI:10.3969/j.issn.1000-7369.2022.05.023]
[2]马玉草,吕 柳,胡 杰,等.基于络病理论探讨干燥综合征的病机与治疗[J].陕西中医,2023,(4):479.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.016]
　MA Yucao,LYU Liu,HU Jie,et al.Discussion on pathogenesis and treatment of sjogren's syndrome based on collateral disease theory[J].,2023,(6):479.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.016]
[3]李红京,宋聪敏,梁笑妍,等.刘启泉基于“通调五脏安脾胃”论治干燥综合征经验[J].陕西中医,2023,(4):503.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.022]
　LI Hongjing,SONG Congmin,LIANG Xiaoyan,et al.Liu Qiquan's experience in treating sjogren syndrome based on the theory of “regulating the five-zang organs to calm the spleen and stomach”[J].,2023,(6):503.[doi:DOI:10.3969/j.issn.1000-7369.2023.04.022]
[4]杨瑞祥,周 全,陈慧敏,等.基于miR-181c-3p/STAT3通路探讨增液润燥汤治疗干燥综合征作用机制[J].陕西中医,2023,(12):1698.[doi:DOI:10.3969/j.issn.1000-7369.2023.12.007]
　YANG Ruixiang,ZHOU Quan,CHEN Huimin,et al.Mechanism of Zengye Runzao decoction in treating sjogren's syndrome based on miR-181c-3p/STAT3 pathway[J].,2023,(6):1698.[doi:DOI:10.3969/j.issn.1000-7369.2023.12.007]
[5]杜彩平,李松伟.基于“上燥治气、下燥治血”理论探讨干燥综合征的病机和辨治[J].陕西中医,2024,(4):516.[doi:DOI:10.3969/j.issn.1000-7369.2024.04.018]
　DU Caiping,LI Songwei.Exploring the pathogenesis and differentiation of Sjogren's syndrome based on the theory of “upper dryness to cure qi,lower dryness to cure blood”[J].,2024,(6):516.[doi:DOI:10.3969/j.issn.1000-7369.2024.04.018]
[6]张 寒,郝梦桃,王可心,等.生腺布液汤对干燥综合征NOD小鼠B细胞活化因子及B细胞活化因子受体表达的影响[J].陕西中医,2024,(8):1036.[doi:DOI:10.3969/j.issn.1000-7369.2024.08.006]
　ZHANG Han,HAO Mengtao,WANG Kexin,et al.Effect of Shengxian Buye decoction on expression of BAFF and BAFFR in NOD mice with sjogren syndrome[J].,2024,(6):1036.[doi:DOI:10.3969/j.issn.1000-7369.2024.08.006]
[7]李 瑞,侯申均,包涵容,等.国医大师张震内外合治干燥综合征经验[J].陕西中医,2025,46(4):542.[doi:DOI:10.3969/j.issn.1000-7369.2025.04.023]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81874438); 北京中医药大学自主课题青年教师项目(2019-JYB-JS-104)
更新日期/Last Update: 2023-06-09