An Jeong Min, Kim EunHye, Lee Ho Jae, Park Min Hee, Son Dong Ju, Hahm Ki Baik
CHA Cancer Preventive Research Center, CHA Bio Complex, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13496, Korea.
Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon, 21565, Korea.
J Clin Biochem Nutr. 2020 Jul;67(1):89-101. doi: 10.3164/jcbn.20-11. Epub 2020 Jun 11.
Gastric stress-related mucosal disease (SRMD) presented from superficial gastritis to deep ulceration consequent to insufficient perfusion, ischemia, and oxidative stress. Though pharmacologic interventions to optimize tissue perfusion or to enhance defensive mechanism are essential, limited clinical outcome necessitates strong acid suppressors or natural agents. Under the hypothesis that L. (NKM 23-1) can enhance defense against SRMD, water immersion restraint stress (WIRS) were imposed to rats and additional groups pretreated with differing doses of NKM 23-1 were monitored. On gross and microscopic evaluation, they significantly rescued SRMD (<0.01). The levels of inflammatory mediators such as IL-18, IL-1β, IL-8, iNOS, TNF-α, caspase-1, NOXs as well as MMPs accompanied with NF-κB p50 activation were all significantly increased in WIRS, but their levels were significantly decreased in Groups pretreated with NKM 23-1. WIRS significantly increased apoptosis, but significantly decreased with NKM 23-1 accompanied with significantly increased levels of cyclin D/E and HSP70/HSP27. Gastric mucin was significantly preserved in Groups pretreated with NKM 23-1, while depleted in WIRS, accompanied with increased expressions of Muc5A. Gastric levels of HO-1 and NQO1 were significantly increased in Group treated with NKM 23-1 with transcriptional activation of Nrf2. Conclusively, preemptive intake of NKM 23-1 significantly rescued SRMD.
胃应激相关黏膜疾病（SRMD）表现为从浅表性胃炎到因灌注不足、缺血和氧化应激导致的深度溃疡。尽管优化组织灌注或增强防御机制的药物干预至关重要，但有限的临床疗效需要强效抑酸剂或天然药物。在L.（NKM 23 - 1）可增强对SRMD防御的假设下，对大鼠施加水浸束缚应激（WIRS），并监测用不同剂量NKM 23 - 1预处理的其他组。通过大体和显微镜评估，它们显著缓解了SRMD（<0.01）。在WIRS中，炎症介质如IL - 18、IL - 1β、IL - 8、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子 - α（TNF - α）、半胱天冬酶 - 1、NADPH氧化酶（NOXs）以及伴随着核因子κB p50激活的基质金属蛋白酶（MMPs）的水平均显著升高，但在用NKM 23 - 1预处理的组中它们的水平显著降低。WIRS显著增加细胞凋亡，但NKM 23 - 1使其显著降低，同时细胞周期蛋白D/E和热休克蛋白70/热休克蛋白27水平显著升高。在用NKM 23 - 1预处理的组中胃黏液显著保留，而在WIRS中减少，同时伴有Muc5A表达增加。在用NKM 23 - 1处理的组中胃血红素加氧酶 - 1（HO - 1）和醌氧化还原酶1（NQO1）水平显著升高，同时核因子E2相关因子2（Nrf2）转录激活。总之，预先摄入NKM 23 - 1显著缓解了SRMD。
