16,16-DIMETHYL PROSTAGLANDIN-E2 PREVENTS THE DEVELOPMENT OF FULMINANT-HEPATITIS AND BLOCKS THE INDUCTION OF MONOCYTE MACROPHAGE PROCOAGULANT ACTIVITY AFTER MURINE HEPATITIS-VIRUS STRAIN-3 INFECTION
16,16-DIMETHYL PROSTAGLANDIN-E2 PREVENTS THE DEVELOPMENT OF FULMINANT-HEPATITIS AND BLOCKS THE INDUCTION OF MONOCYTE MACROPHAGE PROCOAGULANT ACTIVITY AFTER MURINE HEPATITIS-VIRUS STRAIN-3 INFECTION
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DOI：
10.1172/jci113147
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发表时间：
1987-09-01
影响因子：
15.9
通讯作者：
LEVY, GA
中科院分区：
文献类型：
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作者：
ABECASSIS, M;FALK, JA;LEVY, GA
16、16 二甲基前列腺素 E2 (dmPGE2) 是一种已知的细胞保护剂，在暴发性病毒性肝炎、鼠肝炎病毒 3 型 (MHV-3) 实验模型中检查了其改变暴发性肝炎病程的能力。感染 100 50% 致死剂量 (LD50) MHV-3 的完全易感 BABL/cJ 小鼠出现暴发性肝炎的组织学和生化证据，表现为大面积肝坏死伴低血糖、代谢性酸中毒和血清丙氨酸转氨酶 (ALT) 显着升高（平均 1,402 .+-. 619 IU/升）。相比之下，在感染之前或之后（最多48小时）用dmPGE2治疗的动物表现出肝损伤的组织学和生化证据显着减少，其特征是正常的血糖、总CO2和ALT测定（平均ALT，63±40IU/升）。用 PGF2.alpha 治疗受感染的小鼠。表明没有细胞保护作用。在整个感染过程中，从经过 dmPGE2 处理和未处理的动物的肝脏中回收到了高滴度的感染性病毒。在一项平行的体外研究中，dmPGE2 (10-4-10-8 M) 对以 0.1、1.0 和 10.0 感染复数感染的完全易感 BALB/cJ 小鼠分离的培养肝细胞单层显示出类似的细胞保护作用。此外，从受感染和未治疗的 BALB/cJ 小鼠中回收的脾巨噬细胞表现出促凝血活性 (PCA) 较基础 10.+- 显着增强。 5 mU/106 脾巨噬细胞，最多 615 .+-。 102 mU/106 个脾巨噬细胞，而在用 dmPGE2 治疗的感染动物中未检测到巨噬细胞 PCA 增加。这些结果表明，dmPGE2在体内和体外均未显着改变病毒复制或感染性的情况下，对肝细胞具有显着的细胞保护作用，并且在小鼠肝炎病毒3型感染后，在完全易感的BALB/cJ小鼠中阻止体内巨噬细胞PCA的诱导。
16, 16 diemthyl prostaglandin E2 (dmPGE2), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis virus type 3 (MHV-3). Fully susceptible BABL/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 .+-. 619 IU/liter). In contrast, animals treated with dmPGE2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO2, and ALT determinations (mean ALT, 63 .+-. 40 IU/liter). Treatment of infected mice with PGF2.alpha. demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE2-treated and -untreated animals throughout the course of infection. In a parallel in vitro study, dmPGE2 (10-4-10-8 M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 .+-. 5 mU/106 splenic macrophages to a maximum of 615 .+-. 102 mU/106 splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE2. These results suggest that dmPGE2, without detectably altering viral replication or infectivity in vivo, confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro, and prevents the induction of macrophages PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.