The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats

Background

The agent, 2-mercaptoethane sulfonate (MESNA), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide. Because MESNA has potential antioxidant and cytoprotective effects, so we hypothesized that MESNA may protect the brain against traumatic injury.

Method

Thirty-two rats were randomized into four groups of eight animals each; Group 1 (sham), Group 2 (trauma), Group 3 (150 mg/kg MESNA), Group 4 (30 mg/kg methylprednisolone). Only skin incision was performed in the sham group. In all the other groups, the traumatic brain injury model was created by an object weighing 450 g falling freely from a height of 70 cm through a copper tube on to the metal disc over the skull. The drugs were administered immediately after the injury. The animals were killed 24 h later. Brain tissues were extracted for analysis, where levels of tissue malondialdehyde, caspase-3, glutathione peroxidase, superoxide dismutase, nitric oxide, nitric oxide synthetase and xanthine oxidase were analyzed. Also, histopathological evaluation of the tissues was performed.

Results

After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity. Following trauma, both glutathione peroxidase and superoxide dismutase levels were decreased; MESNA increased the activity of both these antioxidant enzymes. Also, after trauma, nitric oxide, nitric oxide synthetase and xanthine oxidase levels were increased; administration of MESNA significantly decreased the levels of nitric oxide, nitric oxide synthetase and xanthine oxidase, promising an antioxidant activity. Histopathological analysis showed that MESNA protected the brain tissues well from injury.

Conclusions

Although further studies considering different dose regimens and time intervals are required, MESNA was shown to be at least as effective as methylprednisolone in the traumatic brain injury model.     

Protective Effect of MESNA (2-Mercaptoethane Sulfonate) Against Hepatic Ischemia/Reperfusion Injury in Rats

Purpose Reoxygenation of ischemic tissue generates various reactive oxygen metabolites (ROMs), which have a deleterious effect on various cellular functions. We evaluated the possible protective effect of 2-mercaptoethane sulfonate (MESNA) on hepatic ischemia/reperfusion (I/R) injury.Methods Wistar albino rats were subjected to 45-min hepatic ischemia, followed by 60-min reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to assess liver function. Liver tissue samples were taken to measure the levels of malondialdehyde (MDA), an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. We also measured hepatic collagen content, as a fibrosis marker.Results Plasma ALT and AST levels were higher in the I/R group than in the control group, but this increase was significantly decreased by MESNA treatment. Hepatic GSH levels, which were significantly depressed by I/R, increased back to the control levels in the MESNA-treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R injury decreased back to the control levels after MESNA treatment. Similarly, the increased hepatic collagen content in the I/R group decreased to the level of the control group after MESNA treatment.Conclusion The fact that MESNA alleviated I/R-induced injury of the liver and improved hepatic structure and function suggests that its antioxidant and oxidant scavenging properties may be of therapeutic value in protecting the liver against oxidative injury caused by I/R.     

Glutamine-induced heat shock protein protects against renal ischaemia-reperfusion injury in rats

Aim: To find out if a single dose of glutamine can relieve acute renal ischaemia‐reperfusion injury in rats, to explore the role of heat shock protein in this process. Methods: Forty‐eight Sprague–Dawley rats were assigned to four groups: saline as control group; glutamine group; quercetin (heat shock protein inhibitor) plus glutamine group; and quercetin plus saline group. The renal ischaemia‐reperfusion rat model was established 1 h after drug administration. Serum creatinine (CR) and blood urea nitrogen (BUN) were analyzed. The kidneys were harvested to evaluate the degree of renal injuries. Heat shock protein expression was detected by immunohistochemistry and western blot. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and apoptosis index was calculated. Results: Statistical data from CR, BUN, haematoxylin–eosin (HE) dyeing and TUNEL assay results showed that ischaemia‐reperfusion injury and cell apoptosis in the glutamine group were significantly milder than those in control group (P < 0.05), while ischaemia‐reperfusion injury and cell apoptosis in the quercetin plus glutamine group and quercetin plus saline group were more severe than those in the control group (P < 0.05). Statistical data from immunohistochemistry and western blot results showed that heat shock protein expression was enhanced in the glutamine group compared with that in the control group (P < 0.01), while it was weaker in the quercetin plus glutamine group and quercetin plus saline group than that in the control group (P < 0.01). Conclusion: Our experiment suggested that a single dose of glutamine could relieve renal ischaemia‐reperfusion injury in rats in 24 h, and its mechanism may be associated with enhanced heat shock protein expression. This finding may provide a new alternative for protecting against clinical renal ischaemia‐reperfusion injury.     

Amino acids protects against renal ischemia-reperfusion injury and attenuates renal endothelin.1 disorder in rats

To investigate nephroprotective effects ofa mixture of 8 L-amino acids on renal ischemia-reperfusioninjury and its effects on renal endothelin-1 (ET-1).     

Rosiglitazone, a PPAR-gamma ligand, protects against burn-induced oxidative injury of remote organs

Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1 beta and TNF-alpha were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.     

Dexmedetomidine protects against burn-induced intestinal barrier injury via the MLCK/p-MLC signalling pathway

BackgroundEvidence suggests that sedative dexmedetomidine can prevent intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. We aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the effects the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury.MethodsIn this study, the plasma concentration of fluorescein isothiocyanate-labelled dextran (FITC-dextran) was measured. Histological changes were evaluated using haematoxylin and eosin (HE) staining. Tight junction proteins were evaluated by western blot and immunofluorescence analyses to assess the structural integrity of intestinal tight junctions. The level of inflammation was detected by enzyme-linked immunosorbent assay (ELISA).ResultsThe results shows that the increase in intestinal permeability caused by burn injury is accompanied by histological damage to the intestine, decreases in the expression of the tight junction proteins Zonula Occludens-1 (ZO-1) and Occludin, increases in inflammatory cytokine levels and elevation of both MLCK protein expression and MLC phosphorylation. After dexmedetomidine treatment, the burn-induced changes were ameliorated.ConclusionsIn conclusion, dexmedetomidine exerted an anti-inflammatory effect and protected tight junction complexes against burn‑induced intestinal barrier damage by inhibiting the MLCK/p-MLC signalling pathways.     

Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury

BACKGROUND: Despite recent advances, severe burn is one of the most common problems faced in the emergency room. Major thermal injury induces the activation of an inflammatory cascade resulting in local tissue damage, to contribute to the development of subsequent damage of multiple organs distant from the original burn wound. OBJECTIVE: Silymarin, the major component of milk thistle has been shown to have antioxidant properties. In the present study, we investigated the putative antioxidant effect of local or systemic silymarin treatment on burn-induced oxidative tissue injury. METHODS: Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce burn. Silymarin either locally (30 mg/kg) applied on 4 cm(2) area or locally+systemically (50 mg/kg, p.o.) was administered after the burn and repeated twice daily. Rats were decapitated 48 h after injury and blood was collected for tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity. In skin tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol-lucigenin chemiluminescense (CL) were measured in addition to the histological evaluation. RESULTS: Burn caused a significant increase in TNF-alpha and LDH levels. MDA levels were increased and GSH levels were decreased in the skin at 48 h after-burn. Both local and systemic silymarin treatments significantly reversed these parameters. The raised MPO activity and luminol-lucigenin CL were also significantly decreased. CONCLUSION: Results indicate that both systemic and local administration of silymarin was effective against burn-induced oxidative damage and morphological alterations in rat skin. Therefore, silymarin merits consideration as a therapeutic agent in the treatment of burns.     

Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.     

Erythropoietin protects against ischaemic acute renal injury.

BACKGROUND: Erythropoietin (EPO) has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental brain injury and cisplatin-induced nephrotoxicity. The aim of the present study was to determine whether EPO administration is also renoprotective in both in vitro and in vivo models of ischaemic acute renal failure. METHODS: Primary cultures of human proximal tubule cells (PTCs) were exposed to either vehicle or EPO (6.25-400 IU/ml) in the presence of hypoxia (1% O(2)), normoxia (21% O(2)) or hypoxia followed by normoxia for up to 24 h. The end-points evaluated included cell apoptosis (morphology and in situ end labelling [ISEL], viability [lactate dehydrogenase (LDH release)], cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA synthesis (thymidine incorporation). The effects of EPO pre-treatment (5000 U/kg) on renal morphology and function were also studied in rat models of unilateral and bilateral ischaemia-reperfusion (IR) injury. RESULTS: In the in vitro model, hypoxia (1% O(2)) induced a significant degree of PTC apoptosis, which was substantially reduced by co-incubation with EPO at 24 h (vehicle 2.5+/-0.5% vs 25 IU/ml EPO 1.8+/-0.4% vs 200 IU/ml EPO 0.9+/-0.2%, n = 9, P<0.05). At high concentrations (400 IU/ml), EPO also stimulated thymidine incorporation in cells exposed to hypoxia with or without subsequent normoxia. LDH release was not significantly affected. In the unilateral IR model, EPO pre-treatment significantly attenuated outer medullary thick ascending limb (TAL) apoptosis (EPO 2.2+/-1.0% of cells vs vehicle 6.5+/-2.2%, P<0.05, n = 5) and potentiated mitosis (EPO 1.1+/-0.3% vs vehicle 0.5+/-0.3%, respectively, P<0.05) within 24 h. EPO-treated rats exhibited enhanced PCNA staining within the proximal straight tubule (6.9+/-0.7% vs vehicle 2.4+/-0.5% vs sham 0.3+/-0.2%, P<0.05), proximal convoluted tubule (2.3+/-0.6% vs vehicle 1.1+/-0.3% vs sham 1.2+/-0.3%, P<0.05) and TAL (4.7+/-0.9% vs vehicle 0.6+/-0.3% vs sham 0.3+/-0.2%, P<0.05). The frequency of tubular profiles with luminal cast material was also reduced (32.0+/-1.6 vs vehicle 37.0+/-1.3%, P = 0.05). EPO-treated rats subjected to bilateral IR injury exhibited similar histological improvements to the unilateral IR injury model, as well as significantly lower peak plasma creatinine concentrations than their vehicle-treated controls (0.04+/-0.01 vs 0.21+/-0.08 mmol/l, respectively, P<0.05). EPO had no effect on renal function in sham-operated controls. CONCLUSIONS: The results suggest that, in addition to its well-known erythropoietic effects, EPO inhibits apoptotic cell death, enhances tubular epithelial regeneration and promotes renal functional recovery in hypoxic or ischaemic acute renal injury.     

Inhibition of sphingosine 1-phosphate receptor 2 protects against renal ischemia-reperfusion injury

Activation of the sphingosine 1-phosphate receptor 1 (S1P(1)R) protects against renal ischemia-reperfusion (IR) injury and inflammation, but the role of other members of this receptor family in modulating renal IR injury is unknown. We found that a selective S1P(2)R antagonist protected against renal IR injury in a dose-dependent manner. Consistent with this observation, both S1P(2)R-deficient mice and wild-type mice treated with S1P(2)R small interfering RNA had reduced renal injury after IR. In contrast, a selective S1P(2)R agonist exacerbated renal IR injury. The S1P(2)R antagonist increased sphingosine kinase-1 (SK1) expression via Rho kinase signaling in renal proximal tubules; the S1P(2)R agonist decreased SK1. S1P(2)R antagonism failed to protect the kidneys of SK1-deficient mice or wild-type mice pretreated with an SK1 inhibitor or an S1P(1)R antagonist, suggesting that the renoprotection conferred by S1P(2)R antagonism results from pathways involving activation of S1P(1)R by SK1. In cultured human proximal tubule (HK-2) cells, the S1P(2)R antagonist selectively upregulated SK1 and attenuated both H(2)O(2)-induced necrosis and TNF-α/cycloheximide-induced apoptosis; the S1P(2)R agonist had the opposite effects. In addition, increased nuclear hypoxia inducible factor-1α was critical in mediating the renoprotective effects of S1P(2)R inhibition. Finally, induction of SK1 and S1P(2)R in response to renal IR and S1P(2)R antagonism occurred selectively in renal proximal tubule cells but not in renal endothelial cells. Taken together, these data suggest that S1P(2)R may be a therapeutic target to attenuate the effects of renal IR injury.     

Exogenous human recombinant interleukin-10 protects the kidney against hypoxia-induced renal injury in immature rats

AIM: The purpose of this study was to determine the effects of exogenous human recombinant interleukin-10 (rhIL-10) on hypoxia-induced renal injury in immature rats. METHOD: The study was performed on 1-day-old Sprague-Dawley rat pups. Group 1 (n = 8) served as non-hypoxic controls. Group 2 (untreated, n = 8) rats were subjected to hypoxia-reoxygenation (H/O) and were then returned to their mothers. Group 3 (rhIL-10 treated, n = 8) rats were subjected to H/O, were returned to their mothers, and were treated with rhIL-10 (75 microg/kg subcutaneously) for the next 3 days. All animals were killed on day 4 and renal specimens were obtained to determine the tissue level of malondialdehyde (MDA) and histological changes. RESULTS: In the untreated group, moderate or severe renal tubular necrosis was observed However, the tubular necrosis score was significantly less in the rhIL-10 treated rats than in the untreated rats (P < 0.05). In the untreated group, MDA levels were significantly increased compared with the control and rhIL-10 groups (P < 0.001 and P < 0.05, respectively). In the rhIL-10 treated group, MDA levels were not significantly different compared with the control group. CONCLUSION: RhIL-10 has a protective effect against hypoxia-induced renal injury in immature rats by depression of tissue MDA level and renal tubular necrosis score.     

Curcumin protects against sepsis-induced acute lung injury in rats

The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.     

异丙酚预先给药对全脑缺血再灌注大鼠脑的保护作用

目的观察异丙酚预先给药对大鼠全脑缺血再灌注后细胞凋亡、脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)mRNA表达的影响,在分子水平上探讨异丙酚对全脑缺血再灌注大鼠脑的保护作用及机制。方法 采用Pulsinelli-Brierley四动脉阻断法制备全脑缺血模型。雄性wistar大鼠57只,体重250-300 g,随机分为假手术组(SH组,n=15);缺血再灌注组(ISC组,n=21);异丙酚预处理组(PPC组,n=21),缺血前静脉注射异丙酚50 mg·kg-1后,用微量泵以1 mg·kg-1·min-1持续静注异丙酚2 h。每组按不同再灌注时间随机分为三个亚组:6 h、24 h、72 h亚组。缺血20 min后,于相应的再灌注时间点断头取脑,脑组织标本切片行HE染色,计数海马CA1区存活细胞数;原位末端标记(TUNEL)法检测凋亡细胞,计算凋亡指数;采用原位杂交技术测定BDNF及TrkB mRNA在海马CAl区表达的阳性率。结果HE染色光镜检查,PPC组海马CAl区锥体细胞核固缩、缺失等改变较ISC组明显减轻。(1)存活细胞数:各6h亚组差异无显著性;ISC及PPC组的24 h、72 h亚组低于SH组,ISC组又低于PPC组(P<0.05)。(2)凋亡细胞指数:ISC组及PPC组的6 h亚组低于24 h、72 h亚组。24 h亚组又低于72 h亚组(P<0.01);ISC组6 h、24 h、72 h亚组均高于SH、PPC组,PPC组6 h亚组与SH组差异无显著性,24 h及7     

褪黑素对大鼠肝脏缺血再灌注损伤的保护作用

探讨褪黑素(MEL)对肝脏缺血再灌注损伤(IRI)的保护作用，在大鼠肝脏热缺血再灌注模型缺血前30min腹腔注射MEL(10mg/kg)，缺血45 min后恢复血流灌注，并于灌注2h, 24h后心腔取血测定血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(AKP)，同时取肝组织行病理组织学检查及细胞凋亡检测。结果缺血再灌注组(IR组)AST，ALT，AKP及肝细胞凋亡数均明显高于正常对照组（N组）(P<0.01)，褪黑素预处理组（MEL组）则明显低于IR组(P<0.05)，而高于N组（P<0.01或0.05）。MEL组肝脏病理组织学改变明显轻于IR组，重于N组。提示MEL对肝缺血再灌注损伤具有保护作用。     

Disruption of guanylyl cyclase-G protects against acute renal injury

The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G(-/-) mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G(-/-) mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-kappaB were lower in GC-G(-/-) mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G(-/-) mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.     

N-乙酰半胱氨酸对大鼠胆道梗阻肝功能损伤的保护作用及机制研究

目的 探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对大鼠胆道梗阻所致肝功能损伤的保护作用及其机制。方法Wistar大鼠72只随机均分成3组：(1)胆道结扎+NAC组(DBL+NAC,n=24)：开腹结扎并切断胆总管,建模成功后经腹腔注射NAC（150 mg·kg-1·d-1）连续注射7 d;(2)胆道结扎组（DBL组,n=24）;(3)假手术组(SO组,n=24)：仅行开腹游离胆总管不予结扎和切断。建模成功后1、3、5、7d每组分别活杀6只大鼠,取静脉血及肝组织,检测肝功能、血浆肿瘤坏死因子α(TNF-α)在各时相点的变化并采用Griess法检测一氧化氮(NO)产生情况。结果 在DBL组、DBL+ NAC组谷-草转氨酶(AST)、血清谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)均随胆道梗阻时间延长而升高,但DBL组AST、ALT在各时间点均较DBL+NAC组明显升高(P＜0.05),而TBIL、DBIL在这两组间无明显差异(P＞0.05)。DBL组和DBL+ NAC组TNF-α、NO浓度变化也随梗阻时间延长而升高,但DBL组较DBL+ NAC组TNF-α、NO浓度升高更明显(P＜0.05)。结论N-乙酰半胱氨酸能有效改善胆道梗阻所致肝损害,并有可能是通过下调肝组织中TNF-α、NO的表达这一途径实现的。