摘要
对Ｗｉｓｔａｒ大鼠体外肝细胞进行了内毒素（ＬＰＳ）及其介质肿瘤坏死因子（ＴＮＦ）等的肝细胞损害机理研究。主要发现是：ＬＰＳ、ＴＮＦα、白细胞介素－１（ＩＬ－１），ＩＬ－６等加入后肝细胞ＬＤＨ漏出及噻唑蓝染色（ＭＴＴ）均无显著变化，仅在肝细胞－Ｋｕｐｆｆｅｒ细胞混合培养组于加入ＬｐＳ、ＬＰＳ／ＴＮＦα后有所变化；经半乳糖胺（ＧａｌＮ）／ＬＰＳ到本内作用后分离的Ｋｕｐｆｆｅｒ细胞与正常肝细胞进行混合培养，加入ＬＰＳ，ＴＮＦ及ＬＰＳ／ＴＮＦα均可致ＬＤＨ漏出显著增高，多粘菌素Ｂ及抗－ＴＮＦ能分别完全和部分阻断此效应；经ＬＰＳ或ＴＮＦα体内作用后抽取的大鼠血清，加入培养肝细胞后均可致ＬＤＨ漏出显著增高与ＭＴＴ显著降低，尤以ＬＰＳ体内作用血清组变化显著经５６℃热灭活后此细胞毒性作用完全消失。上述结果提示，ＬＰＳ与ＴＮＦ等无肝细胞直接毒性作用，而经ＬＰＳ或ＴＮＦ活化的Ｋｕｐｆｆｅｒ细胞可能通过体内一系列瀑布效应，导致肝细胞损害。
his experiment
was carried out to explore the mechanisms of
lipopolysaccharide(LPS)or/and tumor mecrosis factor (TNF)-induced
hepatocyte injury in cultured liver cells in wistar rats. No
signifi-cant changes were found in lactate dehydrogenase(LDH)release
and MTT of hepatocytes after addition of LPS,TNF-α,interleukin(IL)-1
and interlenkin-6, but there were changes in coculture of
hepatocyte-kupffer cell after the addition of LPS and LPS/TNF-α.
When hepatocytes were cocultured with the Kupffer cells from the rats
pre treated with D-galactosamine(GalN)and LPS,increased LDH release
and decreased MTT occured after the additions of LPS,TNF-α and
LPS/TNF-α.The changes could be completely and partially brogated by
polymyxin B and anti-TNF-αin turn.The serum from LPS-or TNF-α
-treated rats,prepared after intravenous administrations of LPS and
TNF-αrespecticely,caused a significant incresase of LDH release and
decrease of MTT of hepatocytes,especially in the serum fron
LPS-treated rats.The cytotoxicity disappeared when the serum from
LPS-or TNF-α-treated rats was pre treated by heating at 56℃for
30min. the above-mentioned results suggest that LPS and cytokines
such as TNF have no direct cytotoxicity on hepatocytes, but the
Kupffer cells activated by LPS or TNF-α may induce hepatocyte injury
through a series of cascade effects in vivo.
出处
《肝脏病杂志》
CSCD
1995年第3期149-151,共3页
