Potential treatment for liver injury through suppression of activated Kupffer cells by PPAR γ

体重约300g的雌性Sprague Dawley大鼠灌胃乙醇（5g/kg BW）， 24h后注射LPS。大鼠肝损伤。吡格他酮是过氧化物酶体增殖激活受体γ (PPARγ)的配体，可防止血浆AST、ALT和TNFα水平升高，但对大鼠血浆和肝脏过氧化脂质水平和血浆内毒素水平没有影响。吡格他酮对乙醇和LPS诱导的肝脏炎症和坏死也有预防作用。吡格他酮可减弱肝脏中乙醇和LPS对TNFα mRNA的诱导作用，但对RXRα mRNA无影响。PPARγ mRNA水平被乙醇和LPS抑制，但被吡格他酮重新捕获。上述结果表明，吡格他酮可能通过抑制TNFα mRNA，至少部分通过NFκ B途径抑制乙醇和LPS诱导的肝损伤。

Female Sprague Dawley rats weighing about 300g were given ethanod (5g/kg BW) intragastncally, and were injected LPS 24h later.Liver injury was induced in this model.Pioghtazone, the ligand for peroxisome proliferates-activated receptor gamma (PPARγ) prevented increase in plasma AST, ALT,and TNFα levels, but not affected on plasma and hepatic levels of lipid peroxide nor plasma endotoxin level in rats.Pioghtazone also prevented hepatic inflammation and necrosis induced by ethanol and LPS.Ethanol and LPS induction of TNFα mRNA in the liver were blunted by Pioghtazone, however, RXRα mRNA were not affected. PPARγ mRNA levels were suppressed by ethanol and LPS, but recaptured by pioghtazone.These results suggest that pioghtazone may prevent liver injury induced by ethanol and LPS by suppression of TNFα mRNA at least partially through NFκ B pathway.