Structural Evolution from Noninterpenetrated to Interpenetrated Thorium-Organic Frameworks Exhibiting High Propyne Storage.

Two thorium-organic frameworks of [Th6O4(OH)4(TFBPDC)6(H2O)6]n (Th-TFBPDC) and [Th6O4(OH)4(TFBPDC)4(HCOO)4(H2O)6]n (Th-TFBPDC-i) constructed from the 3,3',5,5'-tetrakis(fluoro)biphenyl-4,4'-dicarboxylate (TFBPDC2-) ligand were obtained in a reaction. At an early stage of the reaction, the formation of the three-dimensional (3D) framework of Th-TFBPDC was discovered. At a later stage of the reaction, the complete product of Th-TFBPDC-i was obtained. The structural evolution from a noninterpenetrated network of Th-TFBPDC to a 2-fold interpenetrated network of Th-TFBPDC-i is a dissolution-recrystallization process and rationalized as the four equatorial TFBPDC2- ligands in an octahedral [Th6O4(OH)4(TFBPDC)12] unit were displaced by four formate ligands to form a [Th6O4(OH)4(TFBPDC)8(HCOO)4] unit via a ligand substitution reaction. The large pore volume as well as the strong interactions between the host framework and guest propyne (C3H4) molecules demonstrated by computational results endow the highly water-stable Th-TFBPDC with the best-performing C3H4 storage under ambient conditions. This work presents a rare example of structural evolution from a 3D noninterpenetrated network to a 2-fold 3D interpenetrated network and a highly promising metal-organic framework (MOF) for C3H4 storage with a C3H4 uptake of 8.16 mmol g-1 at 298 K.

Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca2+-STIM1/Orai1 Signaling.

Dexmedetomidine (DEX), a potent and highly selective agonist for α2-adrenergic receptors (α2AR), exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca2+ influx. However, the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation (OGD/R) injury in vitro are unknown. We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells, as evidenced by decreased oxidative stress, autophagy, and neuronal apoptosis. Specifically, DEX pretreatment decreased the expression levels of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), and reduced the concentration of intracellular calcium pools. In addition, variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions, which were modulated through STIM1/Orai1 signaling. Moreover, DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3), hallmark markers of autophagy, and the formation of autophagosomes. In conclusion, these results suggested that DEX exerts neuroprotective effects against oxidative stress, autophagy, and neuronal apoptosis after OGD/R injury via modulation of Ca2+-STIM1/Orai1 signaling. Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

Danzhi Jiangtang Capsule Mediates NIT-1 Insulinoma Cell Proliferation and Apoptosis by GLP-1/Akt Signaling Pathway.

OBJECTIVE: This study aimed to investigate the effects of Danzhi Jiangtang Capsule (DJC) on the proliferation and apoptosis functions of NIT-1 pancreatic ß-cells exposed to high-glucose load through GLP-1 activated Akt/ FoxO1 signaling pathway. METHODS: Cellular apoptosis of NIT-1 pancreatic ß-cells was induced by culturing in medium with 33.3mmol/L high glucose (HG). Then low-dose DJC (HG +LD), high-dose DJC (HG +HD), high-dose DJC+ GLP-1 inhibition (HG +HD +GI), and high-dose DJC+AKT inhibition (HG +HD+AI) were added, respectively. Cellular proliferation was accessed by cell counting kit (CCK-8) and cellular apoptosis was measured by Annexin V-FITC/PI staining. The protein levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated AKT (p-AKT), phosphorylated Forkhead box protein O1 (p-FoxO1), and cleaved caspase-3 were detected by Western blotting. The mRNA expression of pancreatic duodenal homeobox-1 (PDX-1), CyclinD1, Bcl-2, and insulin was tested by Q-PCR. RESULTS: Comparing to HG group, (HG+HD) group showed a significantly increased cellular proliferation. The apoptosis of NIT-1 cells also was obviously reduced, with downregulated cleaved caspase-3 protein level and upregulated PDX-1, CyclinD1, and Bcl-2 mRNA levels (P<0.05). Additionally, (HG+HD) group manifested increased insulin mRNA expression; the protein levels of p-PI3K and p-AKT were markedly increased and p-FoxO1 was decreased. All of the above therapeutic effects by DJC intervention had been reversed by GLP-1 inhibition in (HG+HD+GI) group or AKT inhibition in (HG+HD+AI) group. CONCLUSION: DJC was able to attenuate the toxicity of high-glucose load in NIT-1 pancreatic ß-cells, ascribed to the improvement of cellular proliferation and apoptosis by GLP-1/Akt signaling pathway. This study could supply a new mechanism of DJC effects on type 2 diabetes mellitus (T2DM) treatment.

3-N-Butylphthalide mitigates high glucose-induced injury to Schwann cells: association with nitrosation and apoptosis.

A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.

Artesunate restores spatial learning of rats with hepatic encephalopathy by inhibiting ammonia-induced oxidative damage in neurons and dysfunction of glutamate signaling in astroglial cells.

BACKGROUND: Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity. METHODS: HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100mg/kg/day in vivo or added at 50 or 100µM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na+K+-ATPase were measured to indicate the dysfunction of glutamate signaling. RESULTS: Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na+K+-ATPase activity. In contrast, ART, especially at 100µM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro. CONCLUSION: This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions.

PIM1 polymorphism and PIM1 expression as predisposing factors of esophageal squamous cell carcinoma in the Asian population.

Our study aimed to identify the association between a PIM1 polymorphism and PIM1 expression levels with clinicopathological features of esophageal squamous cell carcinoma (ESCC). A total of 168 patients with ESCC were recruited as the case group, and 180 healthy individuals were included as the control group. Polymerase chain reaction-direct sequencing was employed to analyze all genotypes containing the PIM1 -1 882 A>T mutation. Immunohistochemistry was used to detect PIM1 expression. The distributions of genotype AA and allele A of PIM1 -1 882 A>T were higher in the case group than in the control group (both P<0.05). AT + TT carriers had a lower risk of ESCC than AA carriers (P<0.05). PIM1 polymorphism was related to the invasion depth, degree of differentiation, and lymphatic metastasis of ESCC (P<0.05). PIM1 expression was associated with lymphatic metastasis of ESCC and PIM1 polymorphism (both P<0.05). PIM1 -1 882 A>T and the overexpression of PIM1 were associated with the clinicopathological features of ESCC, and PIM1 -1 882 A>T may help to reduce the risk of ESCC in the Asian population.

Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression.

OBJECTIVE: The emergence of side-effect of doxorubicin in cardiomyopathy and heart failure has led to the search for diverse strategies to prevent its cytotoxic effects. This study was to determine the role of obestatin on doxorubicin-induced cardiomyocytes apoptosis and possible underlying mechanism. METHODS: Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6 weeks: group1, untreated normal rats; group2, Doxorubicin-induced heart cardiomyopathy (DC) rats; and group3, obestatin treated HC rats. Doxorubicin (2.5mg/kg) or obestatin (100µg/kg/d) were discontinuously administered via intraperitoneal injection. Primary cardiomyocytes and H9C2 cell line were used for in vitro experiments. Mhrt and Nrf2 (nuclear factor erythroid 2 -related factor 2) mRNA expressions were determined using qRT-PCR. Expression of Nrf2 protein was determined using western blotting. TUNEL assay was performed to evaluate cell apoptosis. RESULTS: Administration of obestatin significantly improved doxorubicin-induced dysfunction of left ventricular contractility function, moreover, resulted in upregulation of Mhrt and Nrf2 in failing myocardial tissue. Co-incubation of obestatin and doxorubicin in primary cardiomyocytes also enhanced Mhrt and Nrf2 expression as well as prevented cell apoptosis in comparison with doxorubicin only. Manipulation of cellular Mhrt by pcDNA-Mhrt or si-Mhrt transfection positively regulated Nrf2 expression in doxorubicin-incubated cardiomyocytes. Silencing Mhrt reversed cardioprotective effects of obestatin both in vivo and in vitro. CONCLUSION: Administration of obestatin attenuates doxorubicin-induced cardiac dysfunction via preservation of cardiomyocytes apoptosis in a Mhrt-Nrf2 dependent pathway.

Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression.

BACKGROUND: Hepatic insulin resistance is a major characteristic of type 2 diabetes mellitus. LncRNA MEG3 has been shown to correlate to hepatic glucose production; however, the underlying mechanism remains unclear. This study aims to investigate the role of MEG3 in hepatic insulin resistance. METHODS: High-fat diet mice, ob/ob mice and mice primary hepatocytes were used in this study. Expression of MEG3, FoxO1, G6pc and Pepck were determined by real-time PCR. FoxO1, G6pc, Pepck, HDAC1 and HDAC3 protein levels were analyzed by western blotting. Hepatic gluconeogenesis, glycogen accumulation, triglyceride and glycogen contents were measured by corresponding assay or kit, and body weight was monitored after an overnight fast. RESULTS: Gene expression of MEG3 was upregulated in high-fat diet and ob/ob mice and increased by palmitate, oleate or linoleate. MEG3 overexpression significantly increased FoxO1, G6pc, Pepck mRNA expressions and hepatic gluconeogenesis and suppressed insulin-stimulated glycogen synthesis in primary hepatocytes, whereas palmitate-induced increase of FoxO1, G6pc and Pepck protein expressions could be reversed by MEG3 interference. In addition, high fat enhanced expression of lncRNA MEG3 in hepatocytes through histone acetylation. Furthermore, MEG3 interference could reverse the up-regulation of triglyceride as well as impaired glucose tolerance and down-regulation of glucogen content in high-fat diet mice or ob/ob mice. CONCLUSION: Upregulation of lncRNA MEG3 enhances hepatic insulin resistance via increasing foxO1expression, suggesting that MEG3 may be a potential target and therapeutic strategy for diabetes.

NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

BACKGROUND: Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. METHODS: Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. RESULTS: Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. CONCLUSION: Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage.

[Effect of danzhi jiangtang capsule combined exercise on the protein expression of NADPH oxidase p22phox in pancreatic tissues of diabetic rats].

OBJECTIVE: To explore effects of exercise combined Danzhi Jiangtang Capsule (DJC) on the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in pancreatic tissues of diabetic rats. METHODS: Sixty male Wistar rats were injected with low dose of streptozotocin and fed with high fat diet to establish a diabetic rat model. The levels of p22phox and 8-hydroxy-2-de-oxyguanosine (8-OHdG) protein in pancreatic tissues were detected by immunohistochemical method, and the level of p22phox protein was also detected by Western blot in the normal group, the model group, the excise group, the DJC group, and the DJC +excise group, respectively. RESULTS: The expression levels of p22phox and 8-OHdG protein in pancreatic tissues were significantly higher in the model group than in the normal group (P <0.01). p22phox and 8-OHdG were mainly expressed in the cytoplasm of pancreatic cells. After administration of exercise or DJC, the expression lev- els of p22phox or 8-OHdG protein in pancreatic tissues decreased significantly (P <0. 01). Exercise combined DJC had synergistic effects in decreasing expressions of p22phox and 8-OHdG (P <0.05). CONCLUSION: Exercise, DJC, and exercise combined DJC could protect islet beta cells by decreasing the expression of NADPH oxidase in beta cells and reducing sources of oxidative stress.

CHOP/ORP150 ratio in endoplasmic reticulum stress: a new mechanism for diabetic peripheral neuropathy.

BACKGROUND/AIMS: Peripheral neuropathy is a frequent and severe diabetic complication characterized by progressive loss of peripheral nerve axons and manifested by pain and eventually complete loss of sensation. Effective therapy for diabetic peripheral neuropathy (DPN) is still lacking due to our limited understanding of the mechanisms for nerve injury. METHODS: Here we tested the roles of endoplasmic reticulum (ER) stress and the ER stress-activated pro-apoptotic protein CHOP and anti-apoptotic protein ORP150 in DPN in a rat model of high-fat/streptozotocin diabetes and in cultured Schwann cells (SCs). RESULTS: No significant DPN was seen in the early stage of diabetes (4 weeks following verification of diabetes). However, after prolonged diabetes (16 weeks following verification of diabetes), DPN was severely developed as reflected by slowed motor and sensory nerve conduction velocity, blunted thermal nociception, and decreased intraepidermal nerve fiber profiles in the hindpaw. Meanwhile, while it was not noticed in sciatic nerves of early diabetes, ER stress in prolonged diabetic rats was indicated by robust increases in H2O2 production and expression of the ER chaperon glucose-regulated protein 78 (GRP78). ORP150 expression was substantially upregulated, accompanied by mild increase in CHOP expression, resulting in a low CHOP/ORP150 ratio, in early diabetes. In contrast, with prolonged diabetes, CHOP expression exceeded ORP150 expression, resulting in an increased CHOP/ORP150 ratio. In vivo knockdown of ORP150 induced DPN in early diabetes and exacerbated the DPN after prolonged diabetes, whereas knockdown of CHOP ameliorated DPN in rats with prolonged diabetic. On the other hand, in vitro knockdown of ORP150 promoted high glucose-induced SC apoptosis, whereas knockdown of CHOP protected SCs from apoptosis. CONCLUSION: Taken together, we have provided evidence for the critical role of ER stress in the development of DN and also uncovered CHOP/ORP150 ratio as an important mechanism for determining neuronal apoptosis during ER stress. In the early stage of diabetes, CHOP/ORP150 ratio was relatively low favoring neuronal cell survival, whereas after prolonged diabetes, CHOP/ORP150 ratio increased resulting in apoptotic cell death leading to accelerated DPN.

[Effects of Chinese herbal medicine Danzhi Jiangtang Capsule and exercise on JNK signaling pathway in pancreatic tissues of diabetic rats].

OBJECTIVE: To explore the effects of exercise and Danzhi Jiangtang Capsule (DJC), a compound traditional herbal medicine, on the JNK signaling pathway in pancreatic tissues of diabetic rats and to investigate the possible mechanisms of exercise and DJC in treating diabetes. METHODS: Seventy-eight male Wistar rats were injected with low dose of streptozotocin and fed a high-fat diet to establish a diabetic model in rats. Then 60 diabetic rats were divided into diabetes group, exercise group, DJC group and exercise combined with DJC group. Another twelve rats were used as normal control. After eight months of treatment, the expression levels of phosphor-c-Jun N-terminal kinase (p-JNK), pancreatic and duodenal homeobox-1 (PDX-1), and insulin protein in pancreatic tissues from rats were detected by immunohistochemical method and Western blotting. RESULTS: In pancreatic tissues of diabetes group, the expression level of p-JNK protein was significantly higher than that in the normal group (P<0.01), and the expression levels of PDX-1 and insulin protein were significantly decreased (P<0.01). After administration of exercise and DJC, the expression level of p-JNK protein in pancreatic tissues of the diabetes group was decreased significantly, while the expression levels of PDX-1 and insulin protein were increased significantly (P<0.05 or P<0.01). CONCLUSION: Exercise and DJC effectively protect isletß-cell function in diabetic rats, which might be due to a decreased JNK signaling pathway.

Protective effect of gliclazide on diabetic peripheral neuropathy through Drp-1 mediated-oxidative stress and apoptosis.

OBJECTIVE: To investigate the protective effect of gliclazide and the role of dynamin-related protein l (Drp-1)-mediated oxidative stress and apoptosis in diabetic peripheral neuropathy (DPN). METHODS: Diabetic rats developed through intra-peritoneal injection of streptozotocin were randomly assigned to treatment group receiving gliclazide or non-treatment group without gliclazide treatment. Rats in control group received intra-peritoneal injection of vehicle and no gliclazide treatment. Eight weeks later, the nerve conduction velocity (NCV) of sciatic nerve was measured and the morphological alterations, the malondialdehyde (MDA) level and superoxide-dismutase (SOD) activity, the expressions of Drp-1, caspase-3, Bax and Bcl-2 in sciatic nerve were evaluated. RESULTS: When compared to rats in control group, rats in non-treatment group showed significantly decrease of NCV, obvious demyelinative alteration of sciatic nerve, increased expressions of Drp-1, caspase-3, Bax, Bcl-2 and MDA, and decreased SOD activity. Compared to rats in non-treatment group, rats in treatment group showed significantly increase of NCV, less demyelination of sciatic nerve, decreased expressions of Drp-1, caspase-3, Bax and MDA, and increased activity of SOD. The expression of Bcl-2 was not significantly different between treatment and non-treatment groups. CONCLUSION: Gliclazide showed protective effect on DPN through modulating Drp-1-mediated oxidative stress and apoptosis.

Changes of Treg-associated molecules on CD4+CD25 +Treg cells in myasthenia gravis and effects of immunosuppressants.

OBJECTIVE: Myasthenia gravis (MG) is a CD4(+) T cell-dependent autoimmune disease, and close attention has been paid to the role of CD4(+)CD25(+)Treg cells (Tregs). Previous results regarding Tregs in MG patients have been conflicting. The discrepancy was partly ascribed to selecting different Treg-associated molecules in defining Tregs. Therefore, we considered it necessary to find a reliable index for assessing the immunologic state in MG patients and explore the effect of IS on them. METHODS: We adopted flow cytometric techniques to measure the numbers and frequencies of Tregs in peripheral blood taken from 57 patients and 91 age-matched healthy donors, and we also analyzed FOXP3 mean fluorescence intensity on Tregs. RESULTS: The number and frequency of Tregs in peripheral blood of MG patients significantly decreased, together with down-regulation of FOXP3 expression. There was dynamic change of Treg cell level and the inverse relationship with clinical symptom, suggesting that the immunologic disorder in MG patients was related to peripheral Tregs population. Meanwhile, CD4(+)CD25(+)FOXP3(+)Helios(+)T cells might be activated Tregs, rather than nTregs. Moreover, the number and frequency of CD4(+)CD25(+)FOXP3(+)Helios(+)T cells significantly decreased in MG patients, indicating that the reduction of the activated Tregs population might be a critical contributor to the pathogenesis of MG. CONCLUSIONS: The significant reduction of the peripheral Tregs population in MG patients might be responsible for the immunologic disorders in MG patients. IS such as GC took its effect possible by increasing the population size, and the underlying mechanism should be further investigated.

[Protective effects of electric stimulation of vagus nerve on acute lung injury in rat with sepsis].

OBJECTIVE: To investigate the protective effect of stimulation of vagus nerve on acute lung injury in rat with sepsis. METHODS: Sepsis was reproduced by cecal ligation and puncture (CLP). Forty male Sprague-Dawley (SD) rats were randomly divided into 4 groups (each n=10): SHAM group received performed sham surgery. In CLP group, CLP was performed. In vagotomy (VGX) group, rats were subjected to bilateral cervical VGX following CLP. In vagus stimulation (STM) group, rats were subjected to bilateral cervical VGX after CLP and the efferent end of the left vagus nerve was stimulated with electric current. The animals were sacrificed at 18 hours after production. Tumor necrosis factor-alpha (TNF-alpha) level in blood was detected, arterial blood lactic acid concentration,pH, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), base excess (BE) and lung wet/drying (W/D) ratio were determined. The histopathology and ultra-microstructure of the lung were observed. RESULTS: The TNF-alpha and lactic acid concentrations, PaCO2 and W/D ratio were all increased, and pH, PaO2, BE all lowered in CLP group and VGX group compared with those of SHAM group (P<0.05 or P<0.01). Compared with CLP group, TNF-alpha, lactic acid concentration,PaCO2,W/D ratio in STM group were decreased obviously, and pH, PaO2 and BE were all increased (P<0.05 or P<0.01). The lung tissue pathology and ultra-microstructure changes indicated that lung injury was severe in CLP group than in SHAM group and was ameliorated in STM group compared with that of CLP group and VGX group. CONCLUSION: The results suggest that direct electrical stimulation of the efferent end of vagus nerve can protect lung against injury induced by sepsis in rat.