不同时间的缺血预处理对脂肪肝缺血再灌注损伤的保护作用

目的探讨缺血预处理（IP）对脂肪肝缺血再灌注（IR）损伤的保护作用,以及取得最佳效果的预处理时间。方法通过建立大鼠脂肪肝模型,给予不同时间的IP（5-10、8-10、10-10、15-10 min）和IR（缺血30 min,再灌注30 min）,检测血清AST、ALT、LDH及NO水平,肝组织中MDA、SOD、MPO含量的变化和肝脏病理学变化。以脂肪肝未行IP组和正常肝脏未行IP组及正常肝脏行10-10 min IP作对照。结果 IR后,脂肪肝未行IP组血清肝功能的变化、肝组织病理学改变及炎性浸润程度显著重于正常肝脏未行IP组。在脂肪肝组中,5或8-10 min IP组血清学及肝组织MDA、MPO水平低于其余组和未行IP组,而其SOD水平显著升高（P〈0.05）。各IP组中的NO水平明显高于其对应的IR组（P〈0.05）。脂肪肝IP组中,5或8-10 min IP组血清NO水平明显高于其余组（P〈0.05）。结论脂肪变性加重肝脏IR损伤,IP对脂肪肝的IR损伤具有保护作用,本实验认为5～8 min缺血和10 min再灌注的IP方案可能是中重度脂肪肝时的最佳预处理方案。     

Abnormal modulation of cell protective systems in response to ischemic/reperfusion injury is important in the development of mouse sickle cell hepatopathy

Background

Sickle cell disease, a genetic red cell disorder inherited in an autosomal recessive manner, occurs throughout the world. Hepatic dysfunction and liver damage may be present in sickle cell disease, but the pathogenesis of these conditions is only partially understood.

Design and Methods

Transgenic mice with sickle cell disease (SAD mice) and wild-type mice were exposed to an ischemic/reperfusion stress. The following parameters were evaluated: hematologic profile, transaminase and bilirubin levels, liver histopathology, and mRNA levels of nuclear factor-κB p65, endothelial nitric oxide synthase, inducible nitric oxide synthase, heme oxygenase-1 and phosphodiesterase-1, -2, -3, and -4 genes in hepatocytes obtained by laser-capture microdissection. Immunoblotting was used to analyze the expression of the following proteins: nuclear factor-κB p65 and phospho-nuclear factor-κB p65, heme oxygenase-1, biliverdin reductase, heat shock protein-70, heat shock protein-27 and peroxiredoxin-6. A subgroup of SAD mice was treated with the phosphodiesterase-4 inhibitor rolipram (30 mg/Kg/day by gavage) during the ischemic/reperfusion protocol.

Results

In SAD mice the ischemic/reperfusion stress induced liver damage compatible with sickle cell disease hepatopathy, which was associated with: (i) lack of hypoxia-induced nuclear factor-κB p65 activation; (ii) imbalance in the endothelial/inducible nitric oxide synthase response to ischemic/reperfusion stress; (iii) lack of hypoxia-induced increased expression of heme oxygenase-1/biliverdin reductase paralleled by a compensatory increased expression of heat shock proteins 70 and 27 and peroxiredoxin-6; and (iv) up-regulation of the phosphodiesterase-1, -2, -3, and -4 genes. In SAD mice the phosphodiesterase-4 inhibitor rolipram attenuated the ischemic/reperfusion-related microcirculatory dysfunction, reduced the inflammatory cell infiltration and induced the heme oxygenase-1/biliverdin reductase cytoprotective systems.

Conclusions

In SAD mice, sickle cell hepatopathy is associated with perturbed nuclear factor-κB p65 signaling with an imbalance of endothelial/inducible nitric oxide synthase levels, lack of heme oxygenase-1/biliverdin reductase expression and up-regulation of two novel cytoprotective systems: heat shock protein-27 and peroxiredoxin-6.     

乌司他丁联合缺血预处理对大鼠肝缺血再灌注损伤的影响

目的探讨乌司他丁(UTI)预处理和缺血预处理(IPC)联合应用对大鼠肝缺血再灌注损伤的影响及可能的作用机制。方法选择雄性SD大鼠50只,随机分为5组,分别为对照(sham)组、缺血再灌注(IR)组、IPC组、UTI组、UTI联合缺血预处理(UCI)组。术后采集下腔静脉血并取肝组织标本,检测血清AST、ALT、TNFɑ,肝组织髓过氧化物酶(MPO)、NF-κB、肝组织湿干比(W/D)及光镜观察肝组织病理形态学变化。计量资料组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果所检测的血清ALT、AST、TNFα水平和肝组织MPO、NF-κB、W/D值,IR组、IPC组、UTI组、UCI组均明显高于sham组(P值均<0.05),而IPC组、UTI组、UCI组均明显低于IR组(P值均<0.05),UTI组明显低于IPC组(P值均<0.05),UCI组明显低于IPC组、UTI组(P值均<0.05)。肝脏病理学检查示IR组、IPC组、UTI组、UCI组与sham组比较,肝组织损伤明显(P值均<0.05),而IPC组、UTI组、UCI组均比IR组肝组织损伤程度轻(P值均<0.05),UTI组肝组织损伤轻于IPC组(P值均<0.05),UCI组肝组织损伤轻于IPC组、UTI组(P值均<0.05)。结论 UTI和UCI对肝脏缺血再灌注损伤均有保护作用,二者联合应用时,明显增强了对肝脏缺血再灌注损伤的保护效应。其发生机制可能与抑制了NF-κB表达,减少TNFɑ、MPO的释放,减轻了肝脏的炎症反应有关。     

Expression of iNOS in early injury in a rat model of small-for-size liver transplantation

BACKGROUND:Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease.Large amounts of nitric oxide generated by inducible nitric oxide synthase(iNOS)have been shown to play an important role in many inflammatory and immune reactions,but expression of iNOS in small-for-size liver transplantation is unknown.The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of sma...     

Influence of inducible nitric oxide synthase polymorphisms in Japanese patients with non-alcoholic fatty liver disease

Aim:  Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD.
Methods:  A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
Results:  We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P -value in the allele frequency model ( P  = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32–0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
Conclusion:  This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.     

Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury

Background:

Liver transplantation involves a period of ischemia and reperfusion to the graft which leads to primary non-function and dysfunction of the liver in 5–10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood flow. We hypothesized that RIPC may directly modulate hepatic microcirculation and have investigated this using intravital microscopy.

Methods:

A rat model of liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were studied (n= 6, each group). Intravital microscopy was used to measure red blood cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils and cell death using propidium iodide.

Results:

RIPC reduced the effects of IRI by significantly increasing red blood cell velocity, sinusoidal flow and sinusoidal perfusion along with decreased neutrophil adhesion and cell death.

Conclusions:

Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function.     

Outcomes and mechanisms of ischemic preconditioning in liver transplantation

BACKGROUND: Liver transplantation is so far the most effective therapeutic modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury represents a critical barrier to liver transplantation. Primary graft dysfunction and small-for-size syndrome are closely associated with I/R injury. Ischemic preconditioning (IPC) is defined as a brief period of liver ischemia followed by reperfusion, and has demonstrated protections against a prolonged I/R injury and improved the capacity of regeneration. ...     

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia／reperfusion injury in rats

AIM: To investigate effects of ischemic pre-conditioning on the liver endogenous oxidant-antioxidant system during ischemia/reperfusion injury. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into sham-operated (Sham), ischemia/ reperfusion (I/R), ischemic pre-conditioning plus ischemia/ reperfusion (IPC) groups. Serum ALT, AST and hyaluronic acid levels were assayed and pathologic alterations observed. Liver malondialdehyde (MDA) contents, endogenous antioxidant enzymes, superoxidase dismutase (SOD), catalase (CAT), gultathionine peroxidase (GSH-Px) activities, neutrophils accumulation marker, myeloperoxidase (MPO) activities were measured respectively. RESULTS: Compared with I/R group, sinusoidal endothelial cells as well as hepatocytes damages, as assessed biochemically and histochemically, were improved significantly in IPC group; neutrophils infiltration was also markedly reduced. In IPC group, liver peroxidation, as measured by MDA contents, was significantly decreased when compared with I/R group; endogenous antioxidant enzymes, SOD, CAT and GSH-Px activities were markedly higher than that in I/R group. CONCLUSION: Ischemic pre-conditioning exerts protective effects on both hepatic sinusoidal endothelial cells and hepatocytes during liver I/R injury. Its mechanisms may involve dimunition of neutrophils infiltration and modulation of the imbalance of endogenous oxidant-antioxidant system in the organism.     

大鼠脑缺血／再灌注损伤热休克蛋白70表达及川芎嗪干预

目的研究大鼠脑缺血／再灌注时热休克蛋白（ＨＳＰ）７０表达及川芎嗪对ＨＳＰ７０表达的影响。方法采用ＳＤ大鼠左侧颈总动脉结扎并滴注生理盐水脑缺血／再灌注模型，以免疫细胞化学法检测２４只缺血／再灌注及川芎嗪干预大鼠脑缺血／再灌注３０ｍｉｎ时脑组织ＨＳＰ７０表达并与病理组织学改变进行对照研究。结果（１）非缺血侧脑组织无ＨＳＰ７０表达，缺血３０ｍｉｎ缺血侧大脑皮层可见ＨＳＰ７０表达；再灌注３０ｍｉｎ组仅１只大鼠（１／６）缺血侧大脑皮层有ＨＳＰ７０表达。（２）与单纯缺血大鼠相比，川芎嗪干预组缺血侧大脑皮层ＨＳＰ７０表达明显增强，计算机辅助图像半定量分析ＨＳＰ７０免疫阳性细胞数，分别为平均４３．５５±１２．５１个／片和８４．９５±１６．７个／片（Ｐ＜０．０１）。（３）缺血侧皮层神经细胞呈现轻度缺血改变，川芎嗪干预大鼠缺血损伤程度似有减轻。结论脑缺血时可诱导缺血脑细胞部分ＨＳＰ７０表达，川芎嗪干预可促使缺血大脑皮层ＨＳＰ７０表达明显增强，皮层神经细胞的缺血损伤有所减轻。     

Tumor necrosis factor suppression and microcirculatory disturbance amelioration in ischemia/reperfusion injury of rat liver after ischemic preconditioning

BACKGROUND: Brief periods of hepatic ischemia produce immediate tolerance for subsequent prolonged ischemia. Although the beneficial effect of this ischemic preconditioning is recognized, the mechanism itself remains poorly understood. METHODS: Male Wistar rats were divided into two groups: a control group that was subjected to 30 min of ischemia + following reperfusion, and an ischemic preconditioning group that was subjected to 5 min of ischemia + 5 min of reperfusion + 30 min of ischemia + following reperfusion. By using this model, hepatic damage, microcirculatory disturbances, and tumor necrosis factor-alpha protein production and mRNA expression were analyzed during the course of reperfusion in both groups. For the hepatic damage evaluations, hepatic enzyme levels, histology, apoptosis analysis, and intravital microfluorography for dead cells were examined. For the microcirculatory disturbance analysis, an adhesion molecule and intravital microfluorography for endothelial-adherent leukocytes were examined. RESULTS: In the ischemic preconditioning group, ischemia/reperfusion injuries (shown by hepatic enzymes elevation, histological degeneration, and increases in the number of apoptotic cells and microfluorographic dead cells) were markedly reduced. Moreover, microcirculatory disturbances represented by intercellular adhesion molecule-1 expression and leukocyte adhesion on the endothelium were ameliorated. Tumor necrosis factor-alpha protein production and mRNA expression were also suppressed in the ischemic preconditioning group. CONCLUSION: The suppression of tumor necrosis factor-alpha and the subsequent amelioration of microcirculatory disturbances were observed, suggesting that the mechanism underlying the protective effect of ischemic preconditioning in hepatic ischemia/reperfusion injuries may involve tumor necrosis factor-alpha and microcirculatory regulation.     

去甲肾上腺素预处理对大鼠供心热休克蛋白70、一氧化氮及一氧化氮合酶表达的影响

目的:探讨去甲肾上腺素预处理是否可诱导心肌热休克蛋白70(HSP70)的合成,并研究其对供心一氧化氮(NO)、一氧化氮合酶(NOS)的影响,探讨去甲肾上腺素预处理心肌保护作用机制。方法:Wistar大鼠18只,分为2组:对照组(C,n=9),腹腔注射0.9%氧化钠注射液0.5 mL,24 h后取离体心脏灌注(Histidine-tryptophan-ketoglutarte,HTK)心脏保护液,4℃保存3 h后建立Langendorff离体心脏灌注模型,灌注(Krebs-Henseleit,K-H)液2 h;实验组(E,n=9)腹腔注射重酒石酸去甲肾上腺素(溶于0.9%氯化钠液中)3.1μmol/kg(0.53 mg/kg),腹腔注射24 h后取离体心脏,处理方法同C组。测定心肌HSP70、NO、NOS的含量以及相关生化指标并做统计学处理比较。结果:HSP70含量E组较C组明显增高(P<0.01),NO、NOS的含量E组较C组明显增多(P<0.01),生化指标E组明显优于C组。结论:去甲肾上腺素预处理能诱导供心心肌组织HSP70、NO、NOS高表达,其对供心具有明显的保护效应,并且其促进心肌NO、NOS的表达,这可能是去甲肾上腺素预处理发挥供心保护作用的机制之一。     

Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats

BACKGROUND:Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury(HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning(HP)is considered to have protective effects on HIRI.This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS:A modified orthotopic liver autotransplantation model was used to simulate HIRI.Sprague-Dawley rats were randomly di...     

缺血预处理减轻肥厚心肌缺血再灌注损伤及其信号途径

目的探讨缺血预处理(IPC)对肥厚心肌体外缺血再灌注(IR)损伤的影响及其信号机制。方法48只心肌肥厚大鼠随机分为4组:IR对照组I、PC组I、PC加磷脂酰肌醇-3激酶(PI3K)抑制剂Wortmannin处理组、Wortmannin处理对照组,观察IPC对心肌肥厚大鼠体外IR心脏左心室收缩压、冠状动脉流量、肌酸磷酸激酶(CPK)和乳酸脱氢酶(LDH)释放、心肌梗死范围以及心肌蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)磷酸化的影响。结果与IR对照组比较,IPC组心脏左心室收缩压、冠状动脉流量显著提高,CPK、LDH释放减少,心肌梗死范围减小,心肌Akt、GSK-3β磷酸化水平增高,Wortmannin能够抑制IPC所致的Akt、GSK-3β磷酸化,但只能部分消除IPC的心脏保护效应。结论IPC能够减轻心肌肥厚大鼠体外心脏IR损伤,PI3K、Akt、GSK-3β信号途径参与介导IPC对体外IR肥厚心肌的保护作用。     

Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone

The mucus layer that covers gastric mucosa is a powerful barrier that protects tissues from the hazardous gastric environment; however, the role of each gastric MUC type, such as MUC1, MUC5AC, and MUC6, has not been evaluated. The purpose of this study is to identify the MUC type, which plays a predominant role in this protective process by use of geranylgeranylacetone (GGA), a promising cytoprotective agent. In addition, the mechanism of mucus secretion promoted by GGA was investigated. Rat gastric mucosal damage was provoked using ethanol, and GGA was pretreated 1 hour before ethanol. GGA was found to significantly protect rats from ethanol-induced gastric damage by increasing mucus levels, MUC5AC and MUC6, especially at ethanol-induced ulcer margins, but not by MUC1. When expression of heat shock protein 70 (HSP70) and neuronal nitric oxide synthase (nNOS) was evaluated by Western blotting, both were found to be increased in GGA-treated ethanol rats. In addition, the cytoprotective effect of GGA was blocked by l-NMMA, a nonspecific NOS inhibitor, but not blocked by aminoguanidine, a specific inducible nitric oxide synthase inhibitor, thus indicating the participation of nNOS. In conclusion, GGA protected ethanol-induced gastric damage by upregulating MUC5AC and MUC6 rather than MUC1. In addition, HSP70 and nNOS were found to be involved in GGA cytoprotection, probably by increasing mucus production or secretion.     

Microarray analysis of endothelial differentially expressed genes in liver of cirrhotic rats

BACKGROUND & AIMS: There is a long-standing interest in the identification of endothelial-specific pathways for therapeutic targeting in cirrhosis. Therefore, the aim of this study was to evaluate differences in gene expression patterns between liver endothelial cells (LECs) from control and cirrhotic rats by using microarrays. METHODS: LECs were obtained by isopycnic centrifugation. LECs gene expression was then analyzed on high-density oligonucleotide microarrays. RESULTS: Analysis of gene expression revealed that most of the differentially expressed mRNA in cirrhosis are associated with extracellular matrix remodeling, inflammation, antioxidant/stress response, and cell signaling. CONCLUSIONS: The collective expression changes observed within some functional groups of genes indicate that LECs in cirrhotic livers may contribute to lymphangiogenesis, enhancement of fibrogenesis and inflammatory processes, changes in cell-cell interaction with up-regulation of adherens junction proteins, and alterations in the intrahepatic vascular tone because of the down-regulation of genes involved in vasodilatation.     

Intestinal expressions of eNOSmRNA and iNOSmRNA in rats with acute liver failure

AIM To observe the gene expression change ofeNOSmRNA and iNOSmRNA in the small and largeintestines with acute liver failure(ALF),and to reveal thebiological function of NO on the pathogenesis of ALF andmultiple organs dysfunction at the molecular level.METHODS Sixty male Wistar rats were selected,weighing from 250g to 350g,and divided into 5 groupsrandomly:SO,ALF(6h,12h),L-Arg,L-NAME,L-Arg andL-NAME,each group with 10 rats.The dose of L-Arg was300mg.kg~(-1),and L-NAME was 30mg.kg~(-1),the reagentsdiluted by normal saline were injected through tail vein 30minutes pre-and post-operation.The rats in the ALFgroup were respectively sacrificed postoperatively at 6h,12h,and the rats in the other groups were sacrificedpostoperatively at 6h.The tissues of small and largeIntestines were harvested in 4% psraforaldehydecontaining the reagent of DEPC and fixed at 6h,embeddedin paraffin,and 4μm section was cut.The expression ofeNOSmRNA and INOSmRNA in these tissues wasdetermined with in situ hybridization,and analyzed withthe imaging analysis system of CMM-3 and SPSSstatistical software.RESULTS The expression of eNOSmRNA in the largeIntestine and INOSmRNA in the small and large intestinesIncreased significantly at 6h after ALF,but the expressionof iNOSmRNA in the small and large intestines reducednotably at 12h after ALF(P<0.05);the expression ofeNOSmRNA in the large intestine and iNOSmRNA in thesmall and large intestines decreased significantly with thereagents of L-Arg at 6h ALF,but the expression ofeNOSmRNA and iNOSmRNA in the small and largeintestines decreased totally with the reagents of L-NAMEor association with L-Arg 6h ALF.CONCLUSION The expression of eNOSmRNA in the largeintestine increased notably at the early stage of ALF,NOinduced by the enzyme of eNOS from the transplantationof eNOSmRNA can protect the function of the largeintestine,the high expression of iNOSmRNA is involved inthe damaged function of the small and large intestines.NOprecursor can reduce the expression of iNOSmRNA in the small and large intestines and the damage to intestines;NOS inhibitor or association with NO precursor can totallylower the expression of eNOSmRNA and iNOSmRNA in thesmall and large intestines,it cannot notably influence theNOS inhibitor in the gene expression of eNOSmRNA andiNOSmRNA to supply the additional NO precursor.     

Induction of a 72-kDa heat shock protein and protection against lipopolysaccharide-induced liver injury in cirrhotic rats

BACKGROUND AND AIM: A 70-kDa heat shock protein (stress-inducible HSP70, HSP72) has been reported to be a cytoprotectant in a variety of organs. It has been reported that HSP72 protected non-cirrhotic rats against endotoxemia. However, its cytoprotective effect against endotoxemia in cirrhotic rats has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on lipopolysaccharide (LPS)-induced liver injury in carbon tetrachloride (CCl(4))-induced cirrhotic rats. METHODS: Liver cirrhosis was produced by an 8-week intraperitoneal injection of CCl(4) in male Sprague-Dawley rats. Expression of HSP72 was investigated using western blot analysis. Cirrhotic rats were given an intraperitoneal injection of LPS (10 mg/kg) with or without hyperthermia (42.5 degrees C, 15 min) preconditioning. Liver injury was assessed biochemically (aspartate transaminase, alanine transaminase, bilirubin, lactate dehydrogenase, creatinine) and histologically. The plasma tumor necrosis factor (TNF)-alpha level was determined. RESULTS: Hyperthermia preconditioning induced a 4-fold increase in HSP72 in the cirrhotic rat liver. Pre-induction of HSP72 prevented LPS-induced liver injury, as evaluated using serum biochemical parameters and histology with reduced TNF-alpha response. CONCLUSION: These findings suggest that pre-induction of HSP72 may provide therapeutic strategies for Gram-negative sepsis-induced liver injury in liver cirrhosis.     

川芎嗪对百草枯中毒大鼠肾组织核因子-кB及iNOS表达的影响

目的探讨川芎嗪对急性百草枯中毒大鼠肾损伤时核因子-κB（NF-κB）和诱导型一氧化氮合酶（iNOS）活性的影响。方法将50只SD大鼠随机分成空白组、阴性对照组、阳性对照组、川芎嗪低剂量组和川芎嗪高剂量组,对肾组织标本进行组织病理学检查,同时测定肾组织NF-κB和iNOS活性。结果与阴性对照组相比,川芎嗪低剂量组肾组织病理显示肾间质充血明显减轻,NF—κB和iNOS也降低（P〈0．01）;而川芎嗪高剂量组无明显改善。结论NF-κB及iNOS在百草枯所致大鼠肾损伤中起重要作用,川芎嗪能降低肾组织NF-κB及iNOS水平,减轻百草枯中毒大鼠的肾组织损伤。