Effect Of Endotoxin On Kupffer Cells And Antagonism Of Glycine To Endotoxin

As being shown in many studies, the various experimental liver injuries (induced by carbon tetrachloride, ethanol, etc) and patients with liver diseases resulted in intestinal endotoxemia (IETM). After studying in many animal models and patients with liver diseases, professor Han De-wu found that intestinal endotoxemia can activate the Kupffer cells and make the hepatitis serious and chronic variety, so he put forward the IETM hypothesis. It was said that the secondary liver injure coming from IETM played a decisive role in the occurrence, development of hepatitis. In view to the theory, professor Han thought that blocking the activated Kupffer cells was the most things in the prevention and cure of liver diseases, even though the reduction of IETM was important. To certify the hypothesis, the effect of endotoxin on Kupffer cells in vitro is needed to study and observe further more. Although IETM was found among animals and patients with ALD, we need to diagnosis whether the Kupffer cell activation results from IETM or (and) ethanol. Besides, because the medicine for anti-IETM and Kupffer cell regulation is rare, on the base of our studies, we further observe the effect of glycine on Kupffer cells, and study the all round antagonism mechanism of glycine to IETM.2003The study was carried out in four parts.The first part was the study on effect of endotoxin on Kupffer cell function. There were four experiments in this part, in which the effects of endotoxin (100ng/ml,lug/ml,10ug/ml,50ug/ml) on cultured Kupffer cell phagocytosis, TNF-a secretion , microfilament, microtubules and apoptosis were studied. The results showed : (1) Endotoxin increased Kupffer cell phagocytosis, but the phagocytosis decreased when endotoxin was added in a larger dose or for a long action time. (2) Endotoxin activated Kupffer cells secreting TNF-a. (3) Endotoxin in a small dose elevated the Kupffer cell microfilament and microtubules expression, while in a large dose it reduced microfilament and microtubules expression, and induced their no smooth arrangments. (4) In a large dose, endotoxin could induce Kupffer cell apoptosis.The second part was the study on effect of ethanol on Kupffer cell function. There were four experiments in this part, in which effects of ethanol(100mg%,200mg%,400mg%,800mg%) on cultured Kupffer cell phagocytosis , TNF-a secretion , microfilament and microtubules expression, and membrane fluidity were studied. The results showed: (1) Ethanol depressesed Kupffer cell phagocytosis. (2) Ethanol in a low dose(100mg%) elevated Kupffer cell TNF-a secretion, while it reduced Kupffer cell TNF-a secretion in a large dose(400mg%,800mg%) or for a long action time. (3) Ethanol made Kupffer cell actin in abnormal arrangement. In small amount (lOOmg %), ethanol increased Kupffer cell tublin expression, while it lowered the tublin expression in large amount (400mg%, SOOmg %) or for a long action time . (4) In large amount, ethanol reduced Kupffer cell membrane fluidity.The third part was effect of glycine on endotoxin -activated Kupffer cell function. There were five experiments in the part, in which effects of glycine (lmmol/1, 10mmol/l, 100mmol/l, 300mmol/l) on Kupffer cell phagocytosis, microfilament and microtubules expressions, and antagonism of glycine on2003endotoxin-induced Kupffer cell phagocytosis, TNF-cc secretion, microfilament and microtubules elevation, and apoptosis were studied. The results showed: (1) Glycine depressed Kupffer cell phagocytosis, weakened the microfilament expression and made the microfilament in abnormal arrangement. (2) Glycine antagonized endotoxin induced increase of Kupffer cell phagocytosis, TNF-a secretion, microfilament, microtubules and apoptosis.The fourth part was the study on antagonism mechanism of glycine to endotoxin. There were three experiments in this part,in which effects of glycine on IETM in TAA liver injured rats, mechanism for glycine to reduce IETM, and effect of glycine on the expression of liver LBP-CDu (LBP-mRNA, CD(4-mRNA and CD 14) system in ALD rats we...