Inhibition of the connexin 43 elevation may be involved in the neuroprotective activity of leptin against brain ischemic injury.

Leptin is a multifunctional hormone produced by the ob gene and is secreted by adipocytes that regulate food intake and energy metabolism. Numerous studies demonstrated that leptin is a novel neuroprotective effector, however, the mechanisms are largely unknown. Herein, we demonstrate the protective activities of leptin after ischemic stroke and provide the first evidence for the involvement of the connexin 43 (Cx43) in leptin-mediated neuroprotection. We found that leptin treatment reduces the infarct volume, improves animal behavioral parameters, and inhibits the elevation of Cx43 expression in vivo. In vitro, leptin reverses ischemia-induced SY5Y and U87 cells Cx43 elevation, secreted glutamate levels in medium and SY5Y cell death, these roles could be abolished by leptin receptor blocker. Additionally, leptin administration upregulated the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. Moreover, ERK1/2 inhibitors pretreatment reversed the effects of leptin on Cx43 expression, glutamate levels and cell apoptosis. In conclusion, the present study demonstrated that leptin can reduce the Cx43 expression and cell death both in vivo and in vitro via ERK1/2 signaling pathway. This result provides a novel regulatory signaling pathway of the neuroprotective effects of leptin and may contribute to ischemic brain injury prevention and therapy.

Localized leptin release may be an important mechanism of curcumin action after acute ischemic injuries.

BACKGROUND: Previous studies have demonstrated that both curcumin and leptin are protective factors against acute injuries. Here, we investigated whether leptin and its signaling pathway mediate the protective effects of curcumin. METHODS: A solid dispersion of curcumin-polyvinylpyrrolidone K30 was prepared and administered intraperitoneally. In vivo intestinal ischemia/reperfusion (I/R) injury in mice determined the effects of curcumin administration on inflammation, oxygen radical production, and leptin expression. In vitro studies using the venous epithelial cell line ECV-304 examined hypoxia/reoxygenation-induced leptin expression and release after curcumin administration. Furthermore, the effects on the leptin-regulated ERK1/2 and p38 MAPK signaling pathways were also explored. RESULTS: Intestinal I/R induced marked bowel injuries. Curcumin treatment significantly improved animal survival and reduced the pathologic injuries in the intestines. Furthermore, the elevated intestinal water content and levels of malondialdehyde, interleukin 1ß (IL-1ß) and IL-6 were significantly decreased, but levels of superoxide dismutase increased. Interestingly, we found that the decreased leptin and its receptor Ob-Rb were restored by curcumin administration. In addition, in vitro studies showed that curcumin increased leptin expression and release after hypoxia/reoxygenation-induced cell injuries. Moreover, curcumin treatment restored decreased ERK1/2 phosphorylation (p-ERK1/2) and inhibited overactive p38 (p-p38) after injuries, and the effect was reversed by a leptin-specific antibody or Ob-R blocker. CONCLUSION: These data suggest that leptin and Ob-Rb-dependent ERK and p38 MAPK signaling pathways may be involved in curcumin protection against intestinal I/R injury, and leptin may be a potential target of curcumin in intestinal I/R injury and other related acute diseases.

Leptin administration alleviates ischemic brain injury in mice by reducing oxidative stress and subsequent neuronal apoptosis.

BACKGROUND: Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model. METHODS: The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/leukemia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay. RESULTS: Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury. CONCLUSIONS: Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.

Leptin relieves intestinal ischemia/reperfusion injury by promoting ERK1/2 phosphorylation and the NO signaling pathway.

BACKGROUND: Recently, research has indicated that leptin plays a protective role in traumatic brain and liver injury. We studied the protective effect of leptin on intestinal I/R injury and examined its mechanism by using mice intestinal I/R model and murine peritoneal macrophage hypoxia/reoxygenation (H/R) injury model. METHODS: Leptin was intraperitoneally administrated at 45 minutes after ischemia, then reperfusion for two hours. Cells were treated with different concentrations of leptin at three hours after hypoxia, then reoxygenation for six hours. Mice intestines were harvested for histopathologic properties. The malondialdehyde, nitric oxide (NO), interleukin-6, and total antioxidative capacity were detected according to respective assay kit. Phosphorylated extracellular regulated kinase1/2 (p-ERK1/2) and phosphorylated cytosolic phospholipase A(2) (p-cPLA2) were determined by Western blot assay. RESULTS: Here, we show that leptin reduced intestinal histologic alterations, malondialdehyde and interleukin-6 levels but increased the endogenous leptin expression and NO production in the intestines. Leptin also increased the NO and total antioxidative capacity levels in cells. We further demonstrated that leptin markedly activated ERK1/2 in the intestines and activated ERK1/2 and cPLA2 in the cells. Moreover, the protective effect of leptin against intestinal I/R injury and elevated NO production was attenuated by blocking the ERK1/2 pathway. CONCLUSIONS: These data demonstrate that leptin ameliorated intestinal I/R and peritoneal macrophage H/R injury by enhancing ERK1/2 phosphorylation and promoting the NO production signaling pathway.

Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression.

Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1mg/kg in 200 µL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 µg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37) (4 × 10(-8)mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression.

Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury and represents a potential therapeutic target.

AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60'R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

[Effects of ethyl pyruvate on injuries of sepsis in mice].

OBJECTIVE: To explore the effect of ethyl pyruvate (EP) and alkaline phosphatase (ALP) on injuries of sepsis and the mechanism involved. METHODS: A murine sepsis model of cecal ligation and puncture was reproduced, and 90 male Kunming mice were divided randomly into sham-operation, model and EP-intervention groups. 75 mg/kg EP was intraperitoneally injected in EP groups 1 hour after establishment of model, and the mice in model group were given a same volume of Ringer's solution. The eyeballs were removed in the latter two groups, and mice were sacrificed at 15 minutes and 1, 3 and 6 hours in subgroups of 10 mice each. ALP, uric acid (UA) and ratio of lactic acid and pyruvic acid were determined in serum and homogenized lung tissue by autonomous biochemical analyzer, and pathological changes in intestine were observed by hematoxylin-eosin (HE) staining. RESULTS: Compared with sham-operation group, serum ALP in model groups and EP groups decreased significantly (P<0.05 or P<0.01), and ALP level of EP group was significantly lower than model group at 6 hours after injury (P<0.05). Compared with sham-operation group, serum UA in model group increased significantly at 1 hour, and reached the highest level at 3 hours (both P<0.05) but decreased significantly later. UA in EP group was significantly lower than that in model group at 1 hour and 3 hours (both P<0.05). Lactic acid/pyruvic acid ratio in lung homogenate of EP group was significantly lower than that of the model group at all the time points (all P<0.05). Intestinal structural damages were distinctly improved in EP group compared with model group at 3 hours and 6 hours (both P<0.05 ). CONCLUSION: EP promotes the utilization of serum ALP, decreases serum UA, ameliorates acidosis and intestinal damages, thus exerting a protective effect on sepsis-induced organ injuries.

Heart-type fatty acid-binding protein is a useful marker for organ dysfunction and leptin alleviates sepsis-induced organ injuries by restraining its tissue levels.

Heart-type fatty acid-binding protein (H-FABP) is widely distributed and has been used to diagnose certain diseases. However, its alteration during infection-evoked organ dysfunction, and the potential association between leptin and it in injury or infection has not been investigated. In the current study, serum H-FABP, leptin, C-reactive protein and interleukin-1beta in the patients with pulmonary infection-induced multiple organ dysfunction were detected. Moreover, a mouse model of sepsis was established, and serum alanine transaminase, uric acid, tissue H-FABP, myeloperoxidase, superoxide dismutase activity and histological alterations in lung and intestine were investigated. Serum H-FABP and leptin increased simultaneously and significantly in the patients, and leptin alleviated pulmonary and intestinal injuries by restraining tissue H-FABP secretions in the mouse model of sepsis. Other investigated variables showed different but independent alterations. In conclusion, H-FABP represents a useful diagnostic marker for organ dysfunction, and its association with leptin will be a novel target for emergency aid.

[Role of leptin in hepatic ischemia/reperfusion-induced hepatic injury].

UNLABELLED: OBJECTIVE; To study the changes of leptin after hepatic ischemia/reperfusion (H-I/R) and its effects on H-I/R-induced hepatic injury. METHODS: A 70% H-I/R model of rats was established. The rats were divided into groups with different reperfusion times and sham-operation group. Radioimmunoassay was applied to measure protein levels of leptin in serum and adipose tissues of the rats. Enzyme-colorimetry was used to detect serum alanine transaminase. Hematoxylin-eosin staining and immunohistochemistry were applied to investigate pathological variations and protein expressions of leptin in livers, respectively. RT-PCR was used to detect leptin mRNA expressions in adipose tissues and livers. RESULTS: Compared with the sham-operation group, serum leptin increased significantly in the 60 min ischemia/360 min reperfusion (I60' R360') group; protein level of leptin in adipose tissues increased significantly in the I60'R60' group; serum alanine transaminase increased significantly in all of the four reperfusion groups; protein expressions of leptin in livers increased significantly in the I60'R60' and 160'R240' groups; leptin mRNA expression in adipose tissues decreased significantly in the I60'R150' group; leptin mRNA expression in livers increased significantly in the 160'R60' group; leptin mRNA expressions in livers decreased significantly in the I60'R150', I60'R240' and I60'R360' groups. Pathological investigation showed that hepatic impairments at the early phase of H-I/R were more serious. The impairments at the later phase lessened gradually. CONCLUSION: The change of leptin expressions after H-I/R may be a protective factor to withstand H-I/ R-induced hepatic injury.

[Distribution of leptin expression and its effect on the recovery of sepsis-induced internal disorders].

OBJECTIVE: To explore the distribution of leptin expression and the effect of sepsis on leptin protein and mRNA levels. METHODS: Vital organ samples including hypothalamus, lung, liver, spleen, stomach, duodenum, kidney, epididymal fat pad and testis of normal rats were collected. The mRNA expressions of leptin in those samples were determined by RT-PCR. The sepsis rat model induce by cecal ligation and perforation (CLP) was established, setting groups of sham-operation, CLP model, CLP + intralipid injection, CLP + estradiol injection and CLP + insulin injection, as the latter three groups were set to intervene energy metabolism and neuroendocrine function. Radioimmunoassay was applied to measure serum leptin concentrations in each group at 12 h after injury, while RT-PCR was also used to detect Leptin mRNA expressions in hypothalamus, fat and lung after injury. RESULTS: Leptin mRNA expressions were confirmed in all the above nine vital organs, with the highest in kidney but the lowest in testis. The serum leptin level showed no significant difference between sham operation group and other four groups. Compared with sham operation group, the Leptin mRNA level in CLP group decreased significantly in hypothalamus, fat and lung, while that in the other three groups showed different changes. The effect of intralipid on Leptin mRNA expression was found to be a dual-direction pattern, with central stimulation but peripheral inhibition. CONCLUSION: Leptin is widely expressed in multiple vital organs, and it may be a protective factor to promote recovery of sepsis-induced internal disorders.

[Effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs of rats].

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin.

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.

[p38 MAPK/cPLA2 pathway mediates interleukins release in inflammatory cell model].

OBJECTIVE: To explore the underlying mechanism of lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and IL-6 release via p38 mitogen-activated protein kinase (MAPK) pathway in HeLa cells for further identification of involved down-stream message factors. METHODS: HeLa cells were challenged with LPS to reproduce inflammatory cell model. The activity or expression of p38 MAPK, cytosolic phospholipase A(2) (cPLA(2)) and COX-2, was inhibited with pretreatment of inflammatory HeLa cells with the inhibitors (SB203580, AACOCF(3), NS-398) or transfected with the cPLA(2) antisense oligonucleotide (SK7111), then the activities and/or expression of p38 MAPK, cPLA(2), COX-2, and relationship with levels of IL-1 beta and IL-6 supernatants were determined in each group. RESULTS: SB203580 obviously down-regulated the activities of p38 and cPLA(2), as well as the release of IL-1 beta and IL-6. AACOCF(3) and SK7111 blocked dose-dependently the activity or expression of cPLA(2), IL-1 beta and IL-6 production. However, the expression of COX-2 could hardly be detected in HeLa cells, even after LPS treatment. At the same time, pre-treatment with NS-398 had no effect on IL-1 beta, IL-6 production. CONCLUSION: p38 MAPK/cPLA(2) pathway mediates the expression of IL-1 beta and IL-6 resulting from LPS treatment of HeLa cells, while COX-2, as a down-stream enzyme of cPLA(2) has no effect in this process.

[Leptin decreases post-septic pulmonary and intestinal FABP levels and its mechanism].

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Leptin protects sepsis-induced renal injury and research for its mechanism].

OBJECTIVE: To detect the effect of sepsis on renal function and corresponding enzymes in mice, and to explore the role of leptin in acute inflammation. METHODS: Sepsis was reproduced by cecum ligation and puncture in mice. Serum uric acid (UA) and four enzymes related with synthesis of free radicals in kidney homogenized fluids, myeloperoxidase (MPO), glutathione-S-transferase (GST), xanthine oxidase (XOD) and superoxide dismutase (SOD) were determined with spectrophotometry, and leptin level in kidney was detected by radioimmunoassay. Histopathologic changes in kidney were observed with hematoxylin-eosin staining. RESULTS: Twelve hours after leptin (0.08 mg/kg, i.p.) and indomethacin (8 mg/kg, i.p.) injection, serum UA was significantly decreased [(295.79+/-80.86) micromol/L and (281.78+/-46.35) micromol/L, respectively, vs. sepsis group (474.03+/-75.22) micromol/L]. At the same time, renal leptin levels in leptin injection group [(196.00+/-134.30) microg/g] 12 hours after sepsis and in indomethacin injection group [(169.30+/-132.00) microg/g] 6 hours after sepsis were also significantly higher than sepsis group [(61.65+/-27.29) microg/g]. Six and 12 hours after leptin and indomethacin injection, renal MPO, GST, XOD and SOD activities were affected to certain extent, as the results were not completely inhibited or enhanced. Nevertheless, leptin and indomethacin could promote scavenge and deactivation of free radicals. CONCLUSION: Low dose leptin can ameliorate sepsis-induced renal injury, which may be related with scavenge and deactivation of free radicals in renal cells, and this mechanism is similar with that of indomethacin.

[Effect of intestinal ischemia/reperfusion injury on protein and mRNA levels of orexin-A].

OBJECTIVE: To investigate the effect of intestinal ischemia/reperfusion (I/R) injury on orexin-A levels in plasma and hypothalamus, and to find out the role of orexin-A in acute inflammatory responses. METHODS: Fifty-four SD rats were randomly divided into a sham-operation group and 5 experiment groups. Then we established the intestinal I/R injury model of rats and setup the 5 experiment groups of 60 min ischemia followed by different periods of time for reperfusion. Protein levels of orexin-A in plasma and hypothalamus were measured by radioimmunoassay, and the changes of orexin-A mRNA expression in hypothalamus were detected by RT-PCR. RESULTS: By analyses on the orexin-A levels in plasma of rats before and after injury, no significant change was observed in the 5 experiment groups (P > 0.05), and the 5 groups' post-injury orexin-A levels in plasma and hypothalamus were not significantly different from the sham-operation group's (P > 0.05). However, by comparison with the sham-operation group after injury, the experiment groups were found to have orexin-A mRNA levels in hypothalamus significantly decreased step by step from 60 min ishchemia/30 min reperfusion (160' R30') to 160'R150'; the lowest level was seen at 160'R150'; and at 160'R240' and I60'R360', the level recovered slowly, but it was still lower than that seen in the sham-operation group. CONCLUSION: Orexin-A makes a delayed response to intestinal I/R injury and may function as inflammatory cytokine in the metabolic disorders caused by acute inflammation.

[Changes in serum leptin levels in patients with surgically induced stress responses].

OBJECTIVE: To explore the effect of operative trauma induced stress responses on serum leptin levels. METHODS: Serum samples of patients who had undergone resection of hepatic tumors or cholecystectomy were collected, and highly sensitive radioimmunoassay and enzyme-linked immunoadsorbent assay (ELISA) were used to determine serum levels of leptin, granulocyte-clone stimulating factor (G-CSF), C-reactive protein (CRP) and adrenocorticotropin hormone (ACTH) in the blood of these patients. RESULTS: Compared with self-control before operation, serum leptin levels decreased slightly right after an abdominal operation (T0), it reached the highest level 1 day after operation (T1), and began to decrease from 2 days (T2) to 4 days after operation (T4), but the level was still higher than that before operation. Serum leptin levels of patients undergoing laparoscopic operation showed no significant difference when compared with that of laparotomy patients. G-SF levels decreased significantly after operation in both groups, and didn't recover to the levels before operation from T1 to T4. CRP levels slightly decreased in both groups at T0, but increased significantly higher than the levels before operation from T1 to T4. ACTH levels of decreased significantly in laparotomy patients from T0 to T1, and began to recover on T2, while that of laparoscopic operation patients showed no significant difference before and after operation. CONCLUSION: Serum leptin levels of patients increase significantly and constantly subsequent to operative trauma induced stress responses, but this change has no correlation with that of CRP, G-SF and ACTH.

[Effect of long tubular bone fracture on serum levels of leptin, acute phase proteins and biochemical markers for organ functions].

OBJECTIVE: To investigate the effect of long tubular bone fracture (LTBF) on serum levels of leptin, acute phase proteins and biochemical markers for organ functions, and to look for the role of leptin in traumatic inflammatory responses. METHODS: Serum samples of LTBF patients and normal controls were collected, and immunoassays were used to determine serum levels of leptin and three acute phase proteins, including C-reactive protein (CRP), interleukin-1 (IL-1) and IL-2, and 21 biochemical markers for organ and metabolic functions were measured simultaneously with automatic biochemical analyzer. Correlation between leptin and all the markers was then analyzed. RESULTS: Compared with normal control, serum levels of leptin, CRP, IL-1 and IL-2 increased significantly (all P<0.05), with various degrees of changes in the markers for hepatic, cardiac, renal and metabolic functions. Leptin was independent to all the markers investigated, and it seemed to exert its unique roles. CONCLUSION: Leptin increases significantly in LTBF-induced acute traumatic inflammatory response, showing a comparatively strong responsiveness to the stimulation, and it may play a role as an anti-inflammatory cytokine.

[Correlation analysis of increase in serum level of leptin with that of C reactive protein, troponin T and endothelin in patients with acute myocardial infarction].

OBJECTIVE: To determine serum leptin levels in patients with acute myocardial infarction (AMI) and coronary atherosclerosis (CS), and to analyze its correlation with C reactive protein (CRP), troponin T (TnT) and endothelin (ET). METHODS: Serum samples from confirmed AMI and CS patients were collected. Leptin and ET were assayed with high sensitive radioimmunoassay, TnT was determined with automatic biochemical analyser, and CRP was determined with enzyme-linked immunosorbant assay (ELISA). RESULTS: Compared with normal control group, serum leptin, TnT, CRP and ET levels increased significantly (all P<0.01) in AMI patients. Serum levels of other cytokines, except TnT in CS patients, increased significantly compared with normal control group (all P<0.01). Correlation analysis showed that all the changes were not correlated with each other, each being an independent factor. Only serum TnT levels of AMI and CS patients showed a significant difference (P<0.01). CONCLUSION: Serum leptin levels of both AMI and CS patients increase significantly without a significant difference between each other, and there is no correlation for leptin with CRP, TnT and ET.

[Changes of serum leptin level in pulmonary infection-induced multiple organ dysfunction syndrome].

OBJECTIVE: To determine serum levels of leptin and some related cytokines in severely ill patients, including severe pulmonary infection-induced multiple organ dysfunction syndrome (MODS), acute myocardial infarction (AMI) and arrhythmia (AR), and to explore the possible role of leptin in the pathogenesis and diagnosis of MODS. METHODS: Radioimmunoassay was used to determine leptin, fatty acid binding protein (FABP), transferrin (Ferr) and interleukin-1beta (IL-1beta), and enzyme-linked immuno adsorbent assay (ELISA) was used to assess C reactive protein (CRP). RESULTS: Compared with normal individuals, leptin levels in MODS, AMI and AR patients increased significantly (all P<0.01). CRP and IL-1beta levels also increased significantly in MODS, AMI and AR patients, but the changes were more marked (all P<0.05) in MODS patients than in the patients of other two diseases (both P<0.05). Though FABP and Ferr levels of patients in all the three groups of patients showed a trend toward increase, especially in MODS patients, there was no significant difference between them and normal individuals. CONCLUSION: Serum leptin level increases significantly in pulmonary infection-induced MODS patients with a simultaneous increase of CRP and IL-1beta levels, and the result suggests that leptin plays a possible role in the pathogenesis and prognosis of MODS.