The mechanism of spleen injury in rabbits with acute renal failure.

Immune function disorders are common during acute renal failure (ARF), but the mechanisms are unknown. As the spleen is the largest organ of the immune system, we aimed to observe if there are morphological changes in the spleen in rabbits with ARF. In addition, we tried to explore its mechanism from the perspective of oxygen free radicals, nitric oxide (NO), myeloperoxidase (MPO), and membrane pump activities. ARF animal models were established by either hypodermic injection of 1.3 mL/kg bw 1% HgCl2 or intramuscular injection of 10 mL/kg bw 50% glycerin. Animals were divided into 12 h, 24 h, and 48 h treatment groups with six rabbits in each group. Compared with control animals, congestion was found in the spleen and splenic trabeculae were increased in the two ARF model groups at multiple time points. The malonaldehyde, NO, nitric oxide synthase, and MPO levels in the ARF models were increased compared with the control group at 24 h or 48 h, and the superoxide dismutase and adenosine triphosphatase activities were significantly lower than the levels in the control group at multiple time points. These indices of free radical damage were induced gradually with ARF development, and there were statistically significant differences at different time points. These data suggested that histological damage of spleen during ARF may lead to immune disorders, which might be related to free radical injury, NO excessive release, polymorphonuclear neutrophils (PMN) sequestration, and membrane pump dysfunction.

The mechanism of myocardium and pancreas injury in rabbits with acute renal failure might be related to myeloperoxidase and membrane pump activities.

There is increasing evidence indicating that the distant organ injury is a major contributor of high mortality in patients subjected to acute renal failure (ARF). However, sources and mechanisms that ARF causes distant organ injury remain to be determined. The aim of this study is to explore the mechanism from polymorphonuclear neutrophil (PMN) sequestration and membrane pump suppression. To achieve this, we examined myeloperoxidase (MPO), a marker of PMN accumulation in tissues, and membrane pump activities of heart, pancreas, and kidney in two ARF rabbit models. Rabbits are randomly assigned to control, HgCl(2)-treated, and glycerin-treated groups. ARF animal models are established by hypodermic injection of 1% HgCl(2) with 1.3 mL/kg bodyweight (bw) in HgCl(2)-treated group or intramuscular injection of 50% glycerin with 10 mL/kg bw in glycerin-treated group, respectively, and all animals in each group are further divided into 12 h, 24 h, and 48 h subgroups with each consisting of six rabbits. Six healthy rabbits serve as control group. Results have shown that MPO activities of kidney, myocardium, and pancreas in two model groups were significantly increased than control group at diverse time points. Membrane pump activities of kidney in two model groups are significantly lower than the control group at multiple time points. Moreover, Na(+)-K(+)-, Ca(2+)-, Mg(2+)-, and Ca(2+)-Mg(2+)-ATPase activities of myocardium and pancreas in two model groups are gradually declined with the development of ARF. These findings suggest that PMN sequestration and membrane pump suppression plays an important role in the pathogenesis of ARF and also a major mechanism of myocardium and pancreas injury during the process of ARF.

[Role of intestinal lymphatic in myocardial injury in rats receiving hemorrhage and lipopolysaccharide challenge].

OBJECTIVE: To explore the effect of mesenteric lymph duct ligation in protecting myocardial injury in rats after hemorrhage and lipopolysaccharide (LPS) challenge. METHODS: Wistar rats were randomly divided into the sham group, non-ligation group and ligation group, and the "two-hit" injury model was reproduced by hemorrhage and LPS administration. Mesenteric lymph was blocked by ligating mesenteric lymph duct in ligation group after hemorrhage. After 24 hours of the assault, myocardial tissue was harvested and homogenized. The activity of myeloperoxidase (MPO) and ATPase and the contents of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined in myocardial homogenate. At the same time, myocardium was pathologically studied. Apoptosis cell rate of myocardium was determined by method of terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), the expression of bcl-2 and bax protein was determined by immunohistochemical method. RESULTS: After hemorrhage and LPS challenge, the level of MPO [(0.23+/-0.08) U/g], TNF-alpha [(9.99+/-2.74) microg/g] and IL-6 [(31.57+/-12.71) microg/g] in myocardial homogenate of non-ligation group were significantly higher than those of sham group [MPO: (0.12+/-0.03) U/g, TNF-alpha: (4.17+/-1.35) microg/g, IL-6: (17.86+/-5.17) microg/g, respectively, all P<0.01], and the activity of ATPase was significantly lower. MPO [(0.13+/-0.03) U/g], TNF-alpha [(5.57+/-1.65) microg/g] and IL-6 [(23.24+/-5.95) microg/g] in myocardial homogenate of ligation group were significantly lower (P<0.05 or P<0.01), and the ATPase activity was significantly higher compared with non-ligation group. The apoptosis rate [(22.7+/-6.9)%] and expression of bax protein (104.5+/-11.4) of myocardial cells in non-ligation group were significantly higher compared with sham group [apoptosis rate: (3.8+/-1.2)%, bax protein: 142.1+/-10.9] and ligation group [apoptosis rate: (8.4+/-2.8)%, bax protein: 128.4+/-9.6], and expression of bcl-2 protein of non-ligation group (196.4+/-19.3) was significantly lower than that of sham group (132.2+/-12.3) and ligation group (165.1+/-11.6, all P<0.01). CONCLUSION: The results demonstrate that the mesenteric lymph duct ligation ameliorate the myocardial injury in rats subjected to hemorrhage and LPS by reducing the inflammatory mediators of TNF-alpha and IL-6 levels, upregulating the bcl-2 protein expression and improving membrane ATPase activity of myocardium.

[Changes in lymph circulation in rats with experimental disseminated intravascular coagulation].

OBJECTIVE: To explore changes in lymph circulation in rats with experimental disseminated intravascular coagulation (DIC). METHODS: Thirty-two male Wistar rats were randomly divided into two groups: DIC group and sham-operation group, with 16 rats in each group.In each group, 8 rats were used to observe the lymphatic circulation of intestinal mesentery, and the others were used to observe lymphatic dynamics. Experimental DIC model was replicated by injecting dextran 500 via jugular vein in Wistar rats. The changes in lymph circulation were observed in these rats with lymphology methods. RESULTS: During the phase of DIC, the contractility of mesenteric micro-lymphatic (ML), the intestinal lymph flux, lymphocytes output were obviously decreased, and there was a few monocytes in the lymph fluid, but the lymph fluid viscosity was increased. After treatment with normal saline (NS), the contractility of ML, the intestinal lymph flux, lymphocytes output were obviously increased, and there was a large amount of monocytes in the lymph fluid, with significant difference compared with sham-operation group (all P<0.05). Moreover, the lymph fluid viscosity was decreased compared with sham-operation group (P<0.05). CONCLUSION: The disturbance in lymph circulation mainly includes depression of contractility of lymphatics, the transport function of lymph circulation, and increased lymph fluid viscosity.

[Effects of ligustrazine injection on lymph circulation in rats with acute microcirculation disturbance].

OBJECTIVE: To explore the interferential effect of ligustrazine injection (LI) on lymph circulation in rats with acute microcirculation disturbance (AMD). METHODS: Sixteen Wistar male rats were divided into experimental and control groups. AMD was done by Dextran 500 injection from jugular vein and effects of LI on lymph circulation were observed in these rats by lymphatology methods. RESULTS: During AMD phase, the contractility of mesenteric lymphatic (ML) , the intestinal lymph flux, lymphocytes out put were obviously decreased, and there was little monocytes in the lymph fluid, but the lymph fluid viscosity was increased. After treatment of LI, the contractility of ML, the intestinal lymph flux, lymphocytes out put was obvious increased. There was a lot of monocytes in the lymph fluid and the lymph fluid viscosity was decreased. There were signifcant difference compared with control group (P < 0.05). CONCLUSION: LI can influence the recovery of AMD though enhancing the contractility of ML and the transport function of lymph circulation and decreasing lymph fluid viscosity.