[Effects of glutamine on alpha-sarcomeric actin and its mRNA expression of myocardium in rats with endotoxemia]

Endotoxemia is a serious syndrome resulting in multi-organ failure. Once it happens, the penetration of small intestine epithelium increases, body liquid losses, then effective circulating blood decreases and serious metabolic acidosis, serious hypotension, systolic failure, and even shock may occur. In this pathological process, endotoxin, tumor necrosis alpha and systolic dysfunction play important roles. Nowadays, many studies have been done to resolve the systolic dysfunction, but too much attention had been paid to the followings: the depressions of myocardium caused by tumor necrosis alpha, other inflammatory factors, endotoxin and metabolic acidosis; the disturbance of blood vessel-nerve regulations; nitric oxide (NO)/inducible nitric oxide synthase (iNOS) over-synthesis and the decreased density of beta-receptors in the myocardium and/or their activities. Little attention has been paid to the relationship between alpha sarcmeric actin (alpha-SA) and systolic dysfunction during endotoxemia. Glutamine (Gln) can be metabolized into glutathione, an eliminator of free radical. It has been used in preventing myocardial damage from reperfusion. This study aimed to observe the dynamic changes of alpha-SA and mRNA expressions in rats with endotoxemia and examine the effects of Gln on them.

Classical rat model of endotoxemia was established by intraperitoneal injection of LPS (4 mg/kg, Escherichia coli O55:B5, Sigma). 121 Wistar 18-day-rats were divided into three groups randomly, (1) 0 h control group (normal saline: 1 ml/kg, n = 11). (2) LPS group (LPS: 4 mg/kg, n = 55). (3) Gln group (LPS: 4 mg/kg and immediately 13.64%; Gln: 1 ml/kg, Fresenus, n = 55), Furthermore, LPS and Gln groups were divided into 2, 4, 6, 24 and 72 h time points (n = 11). Each time point of LPS and Gln as well as control rats were anaesthetized at each time point with 1% chloral hydrate injected intraperitoneally at the dosage of 1 ml/kg. Then rats were sacrificed at appoint time, and the hearts were isolated. Eight of them were put in 76 degrees C liquid nitrogen and then frozen in minute 80 degrees C icebox in order to measure the expression of alpha-SA mRNA by RT-PCR. Three of them were fixed in 4% formaldehydum polymerisatum for 12 to 16 h, then the expression of alpha-SA was detected by immunohistochemistry.

(1) Compared to 0 h, the expressions of alpha-SA and mRNA in LPS group were significantly depressed (P < 0.01). In LPS group, the lowest was at 6 - 24 h, while in Gln group, it was postponed to 24 h. At 72 h, there was no difference in expressions of alpha-SA between Gln and 0 h group (P > 0.05). (2) Comparing at same time point, the expressions of alpha-SA were significant higher in Gln group than those in LPS group, while the expressions of alpha-SA mRNA in Gln group were high at 4-72 h. There was, however, no significant difference at early phase (P > 0.05).

Alpha-SA and its mRNA expression were depressed in LPS-induced endotoxemia, especially from 6 to 24 h. It could damage the systolic function. alpha-SA decrease in endotoxemia was due to the inhibited synthesis other than the promoted degradation. Glutamine could inhibit the effects of LPS on both alpha-SA and its mRNA expressions.