Kwon A-Hon, Qiu Zeyu, Tsuji Katsushige, Miyaso Takeshi, Okumura Tadayoshi
Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
Exp Biol Med (Maywood). 2007 Jul;232(7):895-903.
Fibronectins (Fns) are involved in a number of biologic processes, such as cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, and ischemic injury. We investigated the possible mechanism underlying the protective action of plasma Fn (pFn) on endotoxin shock following partial hepatectomy in rats. Lipopolysaccharide (LPS) was administered intravenously to male Sprague-Dawley rats within 48 hrs of 70% hepatectomy. Prior to LPS administration, pFn or human serum albumin was given intravenously. The survival rate of the pFn-treated group was improved markedly compared with that of the controls. The levels of inflammatory cytokines and nitric oxide (NO) in serum were significantly lower in the pFn-treated group than in the control group. Expression of inducible nitric oxide synthase (iNOS) in hepatocytes also was reduced following pFn treatment. The degree of apoptosis and necrosis in the remnant liver was significantly lower in the pFn-treated rats than the controls. Furthermore, pFn pretreatment greatly inhibited the activation of nuclear factor-kappaB (NF-kappaB), caspase 3 and 8 activities, and cytochrome c release, and caused a decrease in mitochondrial Bcl-x(L). Plasma Fn prevents endotoxin-induced liver injury at least in part through inhibition of NF-kappaB activation, which causes the reduction of iNOS expression and NO production by hepatocytes, and through the downregulation of inflammatory cytokines and promotion of Bcl-x(L) expression.
纤连蛋白（Fn）参与多种生物学过程，如细胞黏附、运动、分化、凋亡、止血、伤口愈合和缺血性损伤。我们研究了血浆Fn（pFn）对大鼠部分肝切除术后内毒素休克保护作用的潜在机制。在70%肝切除术后48小时内，对雄性Sprague-Dawley大鼠静脉注射脂多糖（LPS）。在注射LPS之前，静脉注射pFn或人血清白蛋白。与对照组相比，pFn治疗组的存活率显著提高。pFn治疗组血清中炎性细胞因子和一氧化氮（NO）水平明显低于对照组。pFn治疗后肝细胞中诱导型一氧化氮合酶（iNOS）的表达也降低。pFn治疗的大鼠残余肝脏中的凋亡和坏死程度明显低于对照组。此外，pFn预处理极大地抑制了核因子-κB（NF-κB）的激活、半胱天冬酶3和8的活性以及细胞色素c的释放，并导致线粒体Bcl-x（L）减少。血浆Fn至少部分通过抑制NF-κB激活来预防内毒素诱导的肝损伤，NF-κB激活会导致肝细胞中iNOS表达和NO产生减少，还通过下调炎性细胞因子和促进Bcl-x（L）表达来实现。
