Liu Keyue, Yorozuya Toshihiro, Adachi Naoto, Motoki Atsuko, Ninomiya Kanji, Mabuchi Hisao, Iwamoto Noriyuki, Nishibori Masahiro
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Clin Exp Nephrol. 2015 Aug;19(4):562-6. doi: 10.1007/s10157-014-1027-5. Epub 2014 Sep 6.
Inflammatory reactions play an important role in peritoneal sclerosis in patients on peritoneal dialysis. Since histamine affects inflammatory reactions and immune responses, we investigated effects of intraperitoneal administration of histamine on peritonitis induced by mechanical scraping in mice.
After anesthesia, the right peritoneum was scraped 90 times over 1 min, and bilateral peritonea were observed by light microscopy after 7 days.
Thickness of the peritoneal membrane on the right side was 174 ± 77 µm (mean ± SD, n = 8), while that on the left side was 24 ± 19 µm. Intraperitoneal administration of histamine (0.3 or 1.0 mmol/L, 0.5 mL each) twice daily for 7 days after scraping decreased thickness of the right peritoneum to 42 and 43 % of that in saline-injected animals, respectively (P < 0.01), although histamine (0.1 mmol/L) did not affect it. Promethazine (5 nmol, twice daily for 7 days), a histamine H1 receptor antagonist, abolished the amelioration caused by histamine (1.0 mmol/L). Neither ranitidine (15 nmol), a histamine H2 receptor antagonist, nor thioperamide (7.5 nmol), a histamine H3/H4 receptor antagonist, affected the outcome in histamine-treated mice.
These findings indicate that histamine H1 action partly prevents the development of peritoneal fibrosis caused by mechanical scraping.
炎症反应在腹膜透析患者的腹膜硬化中起重要作用。由于组胺会影响炎症反应和免疫反应,我们研究了腹腔注射组胺对小鼠机械刮擦诱导的腹膜炎的影响。
麻醉后,在1分钟内对右侧腹膜刮擦90次,7天后通过光学显微镜观察双侧腹膜。
右侧腹膜厚度为174±77µm(平均值±标准差,n = 8),而左侧为24±19µm。刮擦后每天两次腹腔注射组胺(0.3或1.0 mmol/L,每次0.5 mL),持续7天,右侧腹膜厚度分别降至注射生理盐水动物的42%和43%(P < 0.01),尽管组胺(0.1 mmol/L)未产生影响。组胺H1受体拮抗剂异丙嗪(5 nmol,每天两次,共7天)消除了组胺(1.0 mmol/L)引起的改善作用。组胺H2受体拮抗剂雷尼替丁(15 nmol)和组胺H3/H4受体拮抗剂硫代哌酰胺(7.5 nmol)均未影响组胺处理小鼠的结果。
这些发现表明组胺H1作用部分预防了机械刮擦引起的腹膜纤维化的发展。