Chen Luguang, Ma Chao, Bian Yun, Li Jing, Wang Tiegong, Su Li, Lu Jianping
Department of Radiology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China.
School of Pharmacy, Second Military Medical University, Shanghai, China.
Cell Physiol Biochem. 2017;44(5):2005-2016. doi: 10.1159/000485906. Epub 2017 Dec 11.
BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent.
By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis.
We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival.
Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future.
背景/目的：慢性胰腺炎是一种胰腺炎症性疾病，其特征为进行性组织破坏和纤维化。慢性胰腺炎的发展与免疫细胞失调有关。目前，仍缺乏针对慢性胰腺炎的特异性有效治疗方法。
通过使用L-精氨酸诱导的慢性胰腺炎小鼠模型，我们测试了强羟自由基清除剂氢气在慢性胰腺炎模型中的治疗潜力。通过苏木精-伊红（HE）染色、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色、髓过氧化物酶（MPO）染色和天狼星染色分析组织炎症、损伤和纤维化情况。采用酶联免疫吸附测定（ELISA）和吸光度测定法测定胰腺中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）细胞因子表达水平以及血清淀粉酶和脂肪酶活性。通过流式细胞术分析细胞凋亡、T细胞亚群比例和细胞内活性氧（ROS）水平。采用调节性T细胞（Tregs）过继性转移和CD25中和来验证Tregs在慢性胰腺炎中的作用。
我们发现氢气治疗显著改善了慢性胰腺炎的多种症状。慢性胰腺炎小鼠中Tregs数量减少，而氢气治疗可恢复因给予L-精氨酸而导致的Tregs缺失。去除Tregs消除了氢气治疗对慢性胰腺炎的保护作用。体外研究表明，氢气可阻断Tregs中ROS的产生并促进Tregs存活。
氢气治疗在控制慢性胰腺炎严重程度方面显示出可靠的益处。我们的研究支持未来氢气可作为慢性胰腺炎患者的一种新治疗方法。
