Rafiq Kazi, Fan Yu-Yan, Sherajee Shamshad J, Takahashi Yoshimasa, Matsuura Junji, Hase Naoki, Mori Hirohito, Nakano Daisuke, Kobara Hideki, Hitomi Hirofumi, Masaki Tsutomu, Urata Hidenori, Nishiyama Akira
1. Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
2. Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., Tokyo, Japan.
Int J Med Sci. 2014 Jan 11;11(3):222-5. doi: 10.7150/ijms.7382. eCollection 2014.
We examined the effects of overexpressed human chymase on survival and activity in lipopolysaccharide (LPS)-treated mice. Human chymase transgenic (Tg) and wild-type C57BL/6 (WT) mice were treated with LPS (0.03, 0.1 and 0.3 mg/day; intraperitoneal) for 2 weeks. Treatment with 0.03 mg LPS did not affect survival in either WT or Tg mice. WT mice were not affected by 0.1 mg/day of LPS, whereas 25% of Tg mice died. Survival of mice treated with 0.3 mg/day of LPS was 87.5% and 0% in WT and Tg, respectively. LPS-induced increases in chymase activity in the heart and skin were significantly greater in Tg than WT mice. These data suggest a possible contribution of human chymase activation to LPS-induced mortality.
我们研究了过表达的人糜蛋白酶对脂多糖(LPS)处理的小鼠存活率和活性的影响。人糜蛋白酶转基因(Tg)小鼠和野生型C57BL/6(WT)小鼠腹腔注射LPS(0.03、0.1和0.3mg/天),持续2周。0.03mg LPS处理对WT或Tg小鼠的存活率均无影响。0.1mg/天的LPS对WT小鼠没有影响,而25%的Tg小鼠死亡。0.3mg/天LPS处理的WT和Tg小鼠的存活率分别为87.5%和0%。LPS诱导的心脏和皮肤中糜蛋白酶活性的增加在Tg小鼠中显著高于WT小鼠。这些数据表明人糜蛋白酶激活可能对LPS诱导的死亡率有影响。