益气解毒利咽方灌胃对放射性唾液腺损伤小鼠的治疗作用及机制  

Therapeutic effect and mechanism of intragastric administration of Yiqi Liyan formula on mice with radioactive salivary gland injury

作　　者：孙丕云 石彧 郭会 于鹏 梁艳艳 吴腾 SUN Piyun;SHI Yu;GUO Hui;YU Peng;LIANG Yanyan;WU Teng(Oncology Department,Liuzhou Traditional Chinese Medicine Hospital(Liuzhou Zhuang Medical Hospital),Liuzhou China)

机构地区：[1]柳州市中医医院(柳州市壮医医院)肿瘤科,广西柳州545001

出　　处：《山东医药》2024年第22期42-46,共5页Shandong Medical Journal

基　　金：广西壮族自治区中医药管理局自筹经费项目(GXZYZ20210026);柳州市科技计划项目(2022CAC0219);广西中医药大学联合基金项目(柳州市中医医院专项)(2023LZ010)。

摘　　要：目的探讨益气解毒利咽方灌胃对放射性唾液腺损伤小鼠的治疗作用及机制。方法采用随机数字表法将60只健康雄性C57BL/6J小鼠分为空白组、模型组、益气解毒利咽方低剂量组(100 mg/kg)和益气解毒利咽方高剂量组(200 mg/kg),各15只。除空白组外,其余小鼠均通过电子直线加速器以15 Gy照射建立放射性唾液腺损伤模型,造模成功后给予相应药物灌胃连续治疗2周。实验结束后,收集分泌唾液;HE染色检测下颌下腺病理结构;透射电镜检测下颌下腺超微结构和自噬体形成;Western blotting法检测下颌下腺组织中c-Jun-N-终端激酶(JNK)、苄氯素1(Beclin 1)、微管相关蛋白ⅠA/ⅠB-轻链3Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ)和自噬抑制因子p62蛋白表达。结果与空白组相比,模型组小鼠下颌下腺重量和唾液分泌量降低;腺泡面积增加,颗粒状曲小管数量减少,导管周围出现纤维化;超微结构出现核焦解、自噬小体形成、内质网破坏以及线粒体肿胀;p-JNK/JNK、Beclin 1蛋白表达和LC3Ⅱ/Ⅰ升高,p62蛋白表达降低(P均<0.05)。与模型组比较,益气解毒利咽方低剂量组和高剂量组小鼠下颌下腺重量和唾液分泌量随给药浓度逐渐增多(P均<0.05);病理和超微结构得到改善,自噬小体形成减少;p-JNK/JNK、Beclin 1和LC3Ⅱ/Ⅰ蛋白表达随药物浓度逐渐降低,p62蛋白表达逐渐升高(P均<0.05)。结论益气解毒利咽方灌胃可能通过激活JNK/Beclin 1通路抑制腺泡细胞自噬,发挥对小鼠放射性唾液腺损伤的改善作用。Objective To investigate the therapeutic effect and mechanism of Yiqi Liyan formula on mice with radio-active salivary gland injury.Methods Sixty healthy male C57BL/6J mice were divided into the blank group,model group,low-dose Yiqi Liyan formula group(100 mg/kg)and high-dose Yiqi Liyan formula group(200 mg/kg),with 15 mice in each.Except for the blank group,all mice were irradiated with 15 Gy through an electron linear gas pedal to es-tablish the radioactive salivary gland injury models,and were given the corresponding drugs by gavage for 2 weeks after successful treatment.At the end of the experiment,secreted saliva was collected;HE staining was used to detect the pathological structure of submandibular gland;transmission electron microscopy was used to examine the ultrastructure of submandibular gland and the formation of autophagosomes;and Western blotting was used to measure the expression lev-els of c-Jun N-terminal kinase(JNK),Beclin 1,LC3-Ⅰ,LC3-Ⅱ,and p62 in the submandibular gland tissues.Results Compared with the blank group,the weight and salivary secretion of the submandibular gland of mice in the model group were reduced;the area of the glandular vesicles increased,the number of granular convoluted tubules de-creased,and fibrosis appeared around the ducts;the ultrastructure showed nuclear pyrolysis,formation of autophagic ves-icles,disruption of the endoplasmic reticulum,and swelling of the mitochondria;and the protein expression levels of p-JNK/JNK,Beclin 1,and LC3Ⅱ/Ⅰincreased,and the expression of p62 protein decreased(all P<0.05).Compared with the model group,the weight of submandibular gland and salivary secretion of mice in the low-dose and high-dose Yiqi Liyan formula groups gradually increased with the concentrations of the drug administered;the pathology and ultra-structure improved,and the formation of autophagic vesicles was reduced;and the protein expression levels of p-JNK/JNK,Beclin 1,and LC3Ⅱ/Ⅰgradually decreased with the concentrations of the drug,and the protein expression

关 键 词：放射性唾液腺损伤 益气解毒利咽方 JNK/Beclin 1通路 细胞自噬 小鼠 

分 类 号：R781.7[医药卫生—口腔医学]