Effect of repeated hypoxic preconditioning on renal ischemia-reperfusion-induced hepatic dysfunction in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of repeated hypoxic preconditioning (RHP) on renal ischemia-reperfusion-induced hepatic dysfunction in rats and the underlying mechanism.</p><p><b>METHODS</b>A total of 120 normal SD rats were randomly divided into 4 groups (n=40), namely RHP surgical group, RHP sham-operated (RHPS) group, nonhypoxic surgical group (IRI group), and nonhypoxic sham-operated group (S group). The rats in the hypoxic groups were exposed to hypoxia in a hypoxic chamber for 5 days prior to establishment of renal ischemia-reperfusion model by resection of the right kidney and clamping the left renal hilum. Serum alanine aminotransferase (ALT), IL-17 A, TNF-a, liver superoxide dismutase (SOD) and nitric oxide (NO) were detected at 2, 8 and 24h after reperfusion, and Western blotting was used to determine the expression of p-PI3K and p-AKT;HE staining was used to observe the structural changes in the liver.</p><p><b>RESULTS</b>Compared with IRI group, RHP group showed significantly milder hepatic damage, lower ALT levels and higher NO levels at 2, 8, and 24 after reperfusion (P<0.05); TNF-a levels were lowered at 24 h (P<0.05) and SOD increased at 8 h after the reperfusion (P<0.05). Compared with S group, IRI group and RHP group showed significantly higher IL-17A levels (P<0.05) but without significant difference between the latter two groups (P>0.05). The expressions of p-PI3K and P-Al<t in RHP group were significantly higher than those in IRI group (P<0.05), especially at 8 h after reperfusion (P<0.05).</p><p><b>CONCLUSION</b>Repeated hypoxic preconditioning can attenuate hepatic injury induced by renal ischemia-reperfusion injury in rats.</p>

Protective effect of leptin against cerebral ischemia/reperfusion injury in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of leptin against cerebral ischemia/reperfusion injury in mice.</p><p><b>METHODS</b>Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and nitric oxide (NO) in the brain tissue were measured by colorimetry. The histopathological changes in the brain were observed with HE staining, and the expression of glial fibrillary acidicprotein (GFAP) was detected by immunohistochemistry.</p><p><b>RESULTS</b>Leptin treatment markedly reduced cerebral infarct volume and neurological deficits induced by transient ischemia. The LDH, MDA and NO levels in the brain tissues were significantly decreased after leptin treatment, which also alleviated the histopathological injury, maintained the normal morphology of the astrocytes and increased the expression of GFAP.</p><p><b>CONCLUSION</b>Leptin produces obvious protective effect against cerebral ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the internal environment and adjusting the activity of the astrocytes.</p>

Changes of leptin levels in serum and myocardium after myocardial ischemia/reperfusion injury / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of rat myocardial ischemia/reperfusion injury on leptin levels in serum and myocardium, and discuss the role of leptin in myocardial ischemia/reperfusion injury.</p><p><b>METHODS</b>A myocardial ischemia/reperfusion injury model of rats was established, serum lactate dehydrogenase (LDH) and leptin levels were detected, and histopathological changes and leptin expressions in myocardium were investigated by hematoxylin-eosin staining and immunohistochemistry, respectively.</p><p><b>RESULTS</b>Serum LDH of ischemia and reperfusion groups increased significantly (P < 0.05), suggesting the model was successfully established and a certain degree of local myocardial injury was induced. Serum leptin of ischemia group (6.34 +/- 2.49) ng/ml was significantly lower than control group (7.50 +/- 2.93 ng/ml, P <0.05). Leptin levels recovered gradually after reperfusion, reached (8.32 +/- 1.74)ng/ml at 2 h after reperfusion, which recovered to the level before injury (8.38 +/- 2.56) ng/ml, and showed a trend to increase as reperfusion time was elongated. Immunohistochemistry results showed that as compared with sham-operation group, myocardial leptin protein expressions of the other four groups were all significantly lower (P < 0.01), and decreased in order by 45 min ischemia/1 h reperfusion, 45 min ischemia/3 h reperfusion, 45 min ischemia and 45 min ischemia/2 h reperfusion.</p><p><b>CONCLUSION</b>Leptin level in the blood decreases significantly at the early 45 min after myocardial ischemia/reperfusion injury, and its expression in myocardium also decreases significantly. There may be a certain relationship between the pathological injury of myocardium and the changes of leptin.</p>

Effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs of rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs, and find out the role leptin plays in acute inflammation.</p><p><b>METHODS</b>A cecal ligation and perforation model of rats was established, setting groups of sham-operation, intralipid injection, injury, estradiol injection and insulin injection. A rat leptin radioimmunoassay was used to check serum leptin concentrations at 12 h after the injury, and RT-PCR was also used to detect leptin mRNA expressions in adipose tissue, lung and liver.</p><p><b>RESULTS</b>Compared with serum leptin level of sham-operation group after injury, that of all the other four groups showed no significant difference, while the level of intralipid group was significantly higher than that of injury group and estradiol group. Compared with leptin mRNA expression level of sham-operation group after injury, that of the other four groups had different changes. Leptin mRNA expression of intralipid group was significantly increased in adipose tissue but decreased in lung and liver.</p><p><b>CONCLUSION</b>Leptin expression levels may be affected by the changes of energy metabolism and neuroendocrine function after injury, which suggests a possible protective role for leptin in the recovery of body homeostasis.</p>

Leptin decreases post-septic pulmonary and intestinal FABP levels and its mechanism / 中国应用生理学杂志

<p><b>AIM</b>To detect the effect of sepsis on fatty acid binding proteins (FABP) levels and corresponding enzymes in lung and intestine of mice, and to explore the role for FABP in acute inflammation.</p><p><b>METHODS</b>A sepsis model of mice made with cecum deligation and perforation was established, and a radioimmunoassay for FABP and 96-well spectrophotometry assays for myeloperoxidase (MPO) and superoxide dismutase (SOD) which were related with clearance of free radicals,were used to detect their levels in lung and intestine homogenized fluids. Hematoxylin-eosin stain was used simultaneously to check the histopathologic chanes of both tissues.</p><p><b>RESULTS</b>Compared with sham group (108.11 +/- 94.03 and 67.22 +/- 19.47 ng/ml) 6 h and 12 h after sepsis, FABP levels in lung and intestine were significantly higher (204.98 +/- 70.72 and 154.29 +/- 60.14 ng/ml), respectively. Twelve hours after leptin (0.1 mg/kg i p) and indomethacin (2 mg/kg i p) injection, lung FABP level decreased and was lower than septic group (P < 0.05). Moreover, 12 h after sepsis intestinal FABP increased, but it decreased after leptin injection (419.80 +/- 80.06 vs 191.09 +/- 96.75 ng/ml), while indomethacin injection had no such effect. MPO and SOD activities in lung and intestine changed accordingly with time after sepsis, the effect of leptin and indomethacin injections on it had no significant correlation with FABP changes.</p><p><b>CONCLUSION</b>Leptin can protect vital organ functions such as lung and intestine after sepsis, as FABP levels, the cellular injury marker, were significantly lower than groups without injection. And this effect might have no correlation with the clearance factors of oxygenic free radicals such as MPO and SOD.</p>

Changes of IL-2, IL-8, IL-10 and TNF-alpha levels in sera of patients with acute graft-versus-host disease / 中国实验血液学杂志

The purpose of this study was to explore the roles of cytokines IL-2, TNF-alpha, IL-10 and IL-8 in the pathogenesis of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The incidence of aGVHD was observed in 33 patients undergoing allogeneic hematopoietic stem cell transplantation. The aGVHD was clinically diagnosed. Sera from the 33 patients were taken before and after allogeneic hematopoietic stem cell transplantation. The IL-2, TNF-alpha, IL-8, IL-10 levels in serum of 33 patients were measured serially by using radioimmuno-assay (RIA). aGVHD occurred in 13 patients including 8 patients with aGVHD I and 5 patients with aGVHD II-IV. The results showed that the circulating levels of IL-2 and TNF-alpha were markedly elevated during aGVHD and strongly correlated with the severity of aGVHD as compared with patients without aGVHD. However, the level of the IL-10 in patients with aGVHD was significantly lower than that in patients without aGVHD. The change of IL-8 level was not significant statistically. It is concluded that IL-2 and TNF-alpha may play important roles in the pathogenesis of aGVHD, and measurement of serum IL-2 and TNF-alpha levels after allo-HSCT can provide predictive indicator for acute GVHD.

Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and investigate the roles of leptin and orexin-A in acute inflammatory responses.</p><p><b>METHODS</b>An intestinal I/R injury rat model was established, and the rats were grouped according to duration of the reperfusion time following a 60-min ischemia. Radioimmunoassay was used to examine the protein levels of leptin in the serum and adipose tissue, and the protein levels of orexin-A in the plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was also performed to detect the mRNA expressions of adipose leptin and hypothalamus orexin-A.</p><p><b>RESULTS</b>Compared with that before injury, serum leptin level of 60-min ischemia with 30-min reperfusion (I60'R30') group decreased significantly and that of I60'R360' increased significantly. Compared with the sham-operation group (sham) after injury, serum leptin level of I60'R360' group increased significantly, and adipose leptin protein levels of I60'R30' and I60'R90' groups decreased significantly, whereas that of I60'R360' group increased obviously. Compared with sham group after injury, adipose leptin mRNA expressions of I60'R30', I60'R240' and I60'R360' groups all increased significantly, while that of I60'R150' showed significant decrease. No significant changes were noted in the protein levels of orexin-A either in the plasma or hypothalamus after I/R injury. In comparison with sham group after injury, hypothalamus orexin-A mRNA expressions of I60'R30' and I60'R90' groups showed gradual but significant decrease, and till 150 min of reperfusion, the expression reached its lowest, followed then by slow recovery at 240 and 360 min, though still remaining significantly lower than that of sham group.</p><p><b>CONCLUSION</b>Leptin and orexin-A have a time-dependent response to intestinal I/R injury, but the former appears to exhibit a faster response, and they may play a certain role in the metabolic disorders of acute inflammation.</p>

Changes of hepatic function in sepsis mice and protective effects of Leptin on it / 第二军医大学学报

Objective: To study the influence of sepsis on hepatic function and corresponding enzymes in mice and to explore the role of Leptin in acute inflammation. Methods: Mice sepsis models were established through cecum ligation and perforation. Mice were divided into sham-operation, sepsis, leptin-protection (peritoneal injection of 0.1 mg/kg Leptin) and indomethacin-protection (peritoneal injection of 2 mg/mg indomethacin) groups. Six and twelve hours after sepsis, leptin levels in liver homogenate were detected by radioimmunoassay; serum alanine aminotransferase (ALT) and 4 enzymes in liver homogenate, myeloperoxidase (MPO), glutathin-S-transferase (GST), xanthine oxidase (XOD) and superoxide dismutase (SOD), all related with synthesis of free radicals, detoxication and purine metabolism, were detected by 96 well spectrophotometry. H-E staining was used to examine the histopathologic changes of liver. Results: Compared with the sham group, sepsis group had an increased serum ALT level (P<0.05) at 12 h after sepsis, but not at 6 h. Serum ALT was significantly lower in Leptin-protection group than in sepsis group 12 h after sepsis (P<0.05). Indomethacin injection had no obvious effect on serum ALT at either 6 h or 12 h after sepsis. Both leptin and indomethacin had no significant effect on hepatic MPO activity, but decreased GST (P<0.01) and SOD (P<0.05) activities and increased XOD (P<0.05) activity. Leptin decreased in sepsis mice but recovered after leptin injection. Indomethacin injection also recovered Leptin level and the level was significantly higher than that of sepsis group at 12 h (P<0.05). Conclusion: Leptin has obviously protective effect on sepsis-induced hepatic injury, the mechanism of which may be related to oxidoreductive reaction, synthesis of oxygen free radicals and detoxication in the metabolic process of hepatic cells.

Interleukin-1beta expression and phospholipase A(2) activation after intestinal ischemia/reperfusion injury / 生理学报

The experiments were carried out to explore the interactions between IL-1 beta gene expression, protein level and phospholipase A(2) PLA(2) inhibition after intestinal ischemia/reperfusion injury. Using a rat intestinal ischemia/reperfusion injury model, after collecting the serum, lung lavage, abdomen cavity lavage and important organ tissue samples from control, injury and PLA(2) inhibitor treated groups, IL-1 beta level was measured by radioimmunoassay, and the mRNA expression of IL-1 beta and type II PLA (2)was determined by RT-PCR. After 6 h of injury, the IL-1 beta level in serum was significantly higher than that in the control group; an increase in IL-1 beta was also observed in abdomen cavity lavage 1 or 3 h after injury. IL-1 beta was significantly increased in liver tissue after injury, but was not changed obviously in the lung, kidney and intestinal tissues. IL-1 beta in the lung lavage was significantly higher than that of control group. The mRNA expression of IL-1 beta in lung tissue was increased after injury, but type II PLA(2) mRNA expression was decreased. There were different changes in IL-1 beta level and gene expression after treatment with PLA(2) inhibitor chloroquine, cyclo-oxidase inhibitor indomethacin, or PAF receptor antagonist SR27417 respectively after injury. All these results indicate that after intestinal ischemia/reperfusion injury, the IL-1 beta level and mRNA gene expression are significantly increased, however, the relationship among IL-1 beta, PLA(2) activation and its metabolite release remains to be further elucidated.