Abecassis M, Falk J A, Makowka L, Dindzans V J, Falk R E, Levy G A
J Clin Invest. 1987 Sep;80(3):881-9. doi: 10.1172/JCI113147.
16, 16 Dimethyl 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 murine hepatitis type 3 (MHV-3). Fully susceptible BALB/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/10(6) splenic macrophages to a maximum of 615 +/- 102 mU/10(6) 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 macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.
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的实验模型——鼠肝炎病毒3型（MHV - 3）所致的暴发性肝炎模型中，对其改变疾病进程的能力进行了研究。完全易感的BALB/cJ小鼠感染100个50%致死剂量（LD50）的MHV - 3后，出现了暴发性肝炎的组织学和生化证据，表现为大量肝坏死，并伴有低血糖、代谢性酸中毒以及血清丙氨酸氨基转移酶（ALT）显著升高（平均值为1,402±619 IU/升）。相比之下，在感染前或感染后（长达48小时）接受dmPGE2治疗的动物，其肝脏损伤的组织学和生化证据均显著减少，表现为血糖、总二氧化碳和ALT测定值正常（ALT平均值为63±40 IU/升）。用前列腺素F2α治疗感染小鼠未显示出细胞保护作用。在整个感染过程中，从接受dmPGE2治疗和未治疗的动物肝脏中均回收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）对来自完全易感的BALB/cJ小鼠、感染复数为0.1、1.0和10.0的分离培养肝细胞单层显示出类似的细胞保护作用。此外，从未经治疗的感染BALB/cJ小鼠中回收的脾巨噬细胞，其促凝活性（PCA）从基础值10±5 mU/10^6脾巨噬细胞显著增加至最大值615±102 mU/10^6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在体内未可检测地改变病毒复制或感染性的情况下，在体内和体外均对肝细胞具有显著的细胞保护作用，并在3型鼠肝炎病毒感染后，防止完全易感的BALB/cJ小鼠体内巨噬细胞PCA的诱导。
