Involvement of ROCK-II in Caerulein-induced Acute Pancreatitis

  • KUSAMA Kazushige
    <I>Second Department of Internal Medicine, Showa University School of Medicine</I>
  • NOZU Fumihiko
    <I>Second Department of Internal Medicine, Showa University School of Medicine</I>
  • AWAI Toshinari
    <I>Second Department of Physiology, Showa University School of Medicine</I>
  • TANAKA Shigeki
    <I>Second Department of Physiology, Showa University School of Medicine</I>
  • HONMA Ikuo
    <I>Second Department of Physiology, Showa University School of Medicine</I>
  • MITAMURA Keiji
    <I>Second Department of Internal Medicine, Showa University School of Medicine</I>

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抄録

We evaluated the role of the Rho effector, ROCK in caeruleininduced acute pancreatitis. To induce acute pancreatitis, caerulein, a CCK (Cholecystokinin) analogue was injected intraperitoneally (IP) every hour for six h, and ROCK-II specific inhibitor, Y-27632, was injected three times by IP 4.5, 6.5, and 8.5 h after the first injection of caerulein. The pancreatic weight ratio did not change significantly in response to either 20μg/kg caerulein alone or a combination of 20μg/kg caerulein and 3 or 30 mg/kg Y-27632. By 12 h after the IP injection of 20μg/kg caerulein and the combination 20μg/kg caerulein and 3 mg/kg Y-27632, the levels of serum amylase increased by 2- to 3-fold over the zero time level. The levels returned to normal by 24 h. Between 9 and 24 h after the combined injection of 20μg/kg caerulein and 30 mg/ kg Y-27632, the levels of serum amylase increased significantly by 5-fold over the zero time and recovered to normal levels by 168 h. Interstitial edema was observed 7 h after the initial IP injection but diminished by 168 h. Mild changes in vacuolization, cell infiltration, and necrosis were observed initially, although these conditions reverted to normal within 168 h. Our data suggest that ROCK-II mediates pancreatic enzyme secretion and prevents acute pancreatitis.

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