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Objective To investigate the therapeutic effect of Dange Jiecheng decoction on a rat model of alcoholic liver disease (ALD) and the anti-oxidative stress mechanism of Dange Jiecheng decoction. Methods A total of 96 Sprague-Dawley rats were randomly divided into blank group with 13 rats and ALD group with 83 rats, and the rats in the ALD group were given liquor by gavage to establish a model of ALD. Then the ALD group was randomly divided into model group, high-dose Dange Jiecheng decoction group (24 g/kg), low-dose Dange Jiecheng decoction group (6 g/kg), and Yiganling tablet group (21 mg/kg), with 17 rats in each group. The rats in the blank group and the model group were given normal saline by gavage, and those in the other groups were given corresponding drugs by gavage, for 4 consecutive weeks. HE staining was used to observe the pathological changes of liver tissue; Western blot was used to measure the contents of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver tissue; quantitative real-time PCR was used to measure the mRNA expression levels of Keap1 and HO-1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the blank group, the model group had disordered arrangement of hepatocytes with necrosis, massive inflammatory cell infiltration, and a large number of lipid droplet vacuoles, significant increases in the protein and mRNA expression levels of Keap1 ( P < 0.05), and significant reductions in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Compared with the model group, the high- and low-dose Dange Jiecheng decoction groups and the Yiganling tablet group had ordered arrangement of hepatocytes, reductions in hepatocyte necrosis and inflammatory cells, and occasional lipid droplet vacuoles, as well as significant reductions in the protein and mRNA expression levels of Keap1 ( P < 0.05) and significant increases in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Conclusion By regulating the Keap1/Nrf2 signaling pathway, Dange Jiecheng decoction can promote the nuclear import of Nrf2, upregulate the expression of HO-1, and alleviate oxidative stress response, thereby exerting a protective effect on ALD rats.
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ObjectiveTo explore the mechanism of plumbagin as a novel ferroptosis inducer in bladder cancer inhibition. MethodBladder cancer T24 cells were used in this study. The effect of different concentrations of plumbagin （0.1， 1， 2， 3， 6， 12， 24， 48 μmol·L-1） on the viability of T24 cells was detected by cell counting kit-8 （CCK-8）. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the apoptosis of T24 cells was detected by annexin V-fluorescein isothiocyanate （Annexin V FITC）/PI apoptosis kit. Different inhibitors （ferroptosis inhibitor Fer-1， apoptosis inhibitor VAD， and necroptosis inhibitor Nec-1） were used in combination with plumbagin （6 μmol·L-1）. Reactive oxygen species （ROS） fluorescent probe （DCFH-DA）， malonaldehyde （MDA）， and glutathione （GSH） kits were used to detect the effects of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the level of ROS and the content of MDA and GSH in T24 cells， respectively. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on peroxide levels in T24 cells was detected by C11-BODIPY fluorescent probe. Western blot was used to detect the effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the protein expression of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， nuclear factor E2-related factor-2 （Nrf-2）， and Kelch-like ECH-associated protein 1 （Keap1）. ResultCompared with the blank group， plumbagin could inhibit the activity of T24 cells （P<0.05） with IC50 of 3.52 μmol·L-1. At the concentrations of 1.5， 3， 6 μmol·L-1， plumbagin significantly promoted the apoptosis of T24 cells （P<0.05） as compared with the blank group. Compared with the plumbagin group at 6 μmol·L-1， the ferroptosis inhibitor and apoptosis inhibitor groups could reverse the inhibitory effect of 6 μmol·L-1 plumbagin on the proliferation of T24 cells （P<0.05）. Compared with the blank group， the plumbagin groups at 1.5， 3， 6 μmol·L-1 showed increased content of ROS， MDA， and lipid peroxides in T24 cells， decreased GSH level， and reduced SLC7A11， GPX4， and Nrf-2/Keap1 （P<0.05）. Conclusionplumbagin can induce ferroptosis， and its mechanism is related to the Nrf-2/Keap1 signaling pathway.
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Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×1010 CFU (CFU: colony forming units) WB800, and 5×1010 CFU WB800-KR32, respectively, on Days 1‒14 and all infused with ETEC K88 1×1010 CFU on Days 15‒17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
Subject(s)
Animals , Swine , Enterotoxigenic Escherichia coli , Kelch-Like ECH-Associated Protein 1 , Bacillus subtilis , NF-E2-Related Factor 2 , Antioxidants , Oxidative StressABSTRACT
Objective@# To explore the effects of red LED light mediated by the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (KEAP1-NRF2/HO-1) pathway on osteogenic differentiation and oxidative stress damage of human periodontal ligament stem cells (hPDLSCs) induced by high glucose, which provides a basis for the application of red light-emitting diode (LED) light in cell antioxidative damage.@*Methods@#hPDLSCs were identified by flow cytometric analysis, alkaline phosphatase (ALP) staining and Alizarin red-S staining; hPDLSCs were pretreated in a high glucose environment for 48 hours and irradiated with 1, 3, or 5 J/cm2 red LED light. A CCK-8 assay was performed to choose the radiant exposure that had the strongest effect on promoting the cell proliferation rate for subsequent experiments. hPDLSCs were divided into a control group, a high glucose group and a high glucose+light exposure group. ALP staining, ALP activity, Alizarin red-S staining and quantitative calcified nodules were used to detect the osteogenic differentiation of hPDLSCs; qRT-PCR and Western blot were used to detect the gene and protein expression levels of ALP, runt-related transcription factor 2 (RUNX2) and osterix (OSX); the relative mRNA expression levels of antioxidant enzyme-related genes superoxide dismutase 2 (SOD2) and catalase (CAT) in hPDLSCs were detected by qRT-PCR; reactive oxygen species (ROS) levels were detected by fluorescence microscopy and flow cytometry; the tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in cell supernatants were detected by ELISA; the NRF2-specific inhibitor ML385 was used to inhibit the NRF2 pathway; ALP staining and ALP activity were used to detect the markers of early osteogenic differentiation; qRT-PCR was used to detect the gene expression of ALP, RUNX2 and OSX; and the protein expression levels of KEAP1, NRF2 and HO-1 were detected by Western blot.@*Results @# Identified, and irradiant exposure of 5 J/cm2 was chosen for subsequent experiments. Red LED light irradiation (5 J/cm2) improved the osteogenic differentiation of hPDLSCs induced by high glucose (P<0.05), increased the mRNA and protein levels of ALP, RUNX2 and OSX (P<0.05), upregulated the mRNA expression levels of SOD2 and CAT (P<0.05), reduced the levels of ROS (P<0.05), and reduced TNF-α and IL-1β levels in the cell supernatants (P<0.05). When ML385 was added to inhibit the NRF2 pathway, the ALP activity of cells was decreased (P<0.05); the gene expression levels of ALP, RUNX2 and OSX were downregulated (P<0.05); the protein level of KEAP1 was upregulated (P<0.05); and the protein levels of NRF2 and HO-1 were downregulated (P<0.05)@*Conclusion@#Red LED light may promote the proliferation and osteoblastic differentiation of hPDLSCs induced by high glucose through the KEAP1-NRF2/HO-1 pathway and reduce the oxidative stress damage to hPDLSCs induced by high glucose.
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The pathological manifestations of neurodegenerative diseases， such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis， are abnormal protein aggregation and accumulation， microglia activation， and mitochondrial dysfunction， which eventually lead to the gradual loss of neuronal structure or function and deteriorate over time. These pathological processes are related to the production of reactive oxygen species （ROS）， which can cause oxidative stress and damage proteins， lipids， and DNA， leading to cell and tissue injuries. The Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is the main mechanism to maintain the redox balance of the body and defend against oxidative stress injury. Nrf2 activates the expression of a series of antioxidant genes related to ARE through the dissociation of Keap1 and nuclear transfer in the cytoplasm to protect the body from oxidative damage. Therefore， the discovery and study of the Keap1/Nrf2/ARE signaling pathway activator is of great significance for the prevention and treatment of neurodegenerative diseases. Because of the remarkable biological activity and slight side effects， natural products are a treasure trove for new drug research and development. Studies have shown that a variety of natural products can activate the Keap1/Nrf2/ARE signaling pathway and play a neuroprotective role. According to the structural characteristics， natural products can be divided into flavonoids， terpenoids， volatile oils， polyphenols， and phenylpropanoids. This study summarized the underlying mechanism of the Keap1/Nrf2/ARE signaling pathway in regulating diseases and reviewed the research progress on natural products based on this signaling pathway in neuroprotection to provide references for the development of clinical drugs for the prevention and treatment of neurodegenerative diseases.
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Oxidative stress(OS)is a major reason for body damage. Studies have shown that a variety of factors, such as ischemia and hypoxia, excessive light and hyperglycemia can cause the increase of reactive oxygen species and free radicals in the retina, thus inducing OS, damaging retina and affecting the normal visual function. Kelch-like ECH-associated protein 1(KEAP1)and nuclear factor erythroid 2 related factor 2(NRF2), which together constitute the main antioxidant stress signaling pathway in the body, play an antioxidant role by regulating retinal energy metabolism and cell proliferation, apoptosis and autophagy through various ways, so as to reduce retinal damage caused by OS. In this paper, the role and mechanism of the KEAP1-NRF2 signaling pathway regulation of OS in the retinal are briefly reviewed, aiming to provide ideas for subsequent research.
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ObjectiveTo study the effect of Buyang Huanwutang on Kelch-like Ech-related protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis （IPF） and explore the mechanism of this prescription in the treatment of IPF. MethodForty SPF-grade male SD rats were assigned into a sham operation group， a model group， a Buyang Huanwutang group， and a nintedanib group according to random number table method， with 10 rats in each group. IPF rat model was established by intratracheal infusion of bleomycin （0.005 g·kg-1） in other groups except the sham operation group. Buyang Huanwutang group was administrated with Buyang Huanwutang (14.84 g·kg-1)，intragastric administration of nitedanib suspension (0.1 g·kg-1)，sham operation group and model group were given equal volume of normal saline， for 28 days. After lung function test， serum and lung tissue samples were collected. Hematoxylin-eosin （HE） staining and Masson trichrome staining were employed to observe the pathological changes of the lung tissue. The content of hydroxyproline （HYP） in lung tissue was detected. The levels of malondialdehyde （MDA） in serum and lung tissue， and the activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and catalase （CAT） were determined. The mRNA and protein levels of Keap1， Nrf2， and HO-1 was determined by Real-time fluorescent quantitative polymerase chain reaction， immunohistochemical staining， and Western blot. ResultCompared with the sham operation group， the modeling increased the resistance and elasticity and decreased the compliance of respiratory system （P<0.01）， elevated the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and enriched MDA in serum and lung tissue， while it decreased the activities of SOD， GSH-Px， and CAT （P<0.01）. Furthermore， the modeling down-regulated the mRNA and protein levels of Keap1 and up-regulated those of Nrf2 and HO-1 in lung tissue （P<0.01）. Compared with the model group， Buyang Huanwutang decreased the resistance and elasticity and increased the compliance of respiratory system （P<0.01）， lowered the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and reduced MDA in serum and lung tissue， while it increased the activities of SOD， GSH-Px， and CAT （P<0.01）. Additionally， Buyang Huanwutang down-regulated the expression of Keap1 and up-regulated that of Nrf2 and HO-1 in lung tissue （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can activate Keap1/Nrf2/HO-1 signaling pathway to enhance the antioxidant capacity and slow down the pathological process of IPF in rats.
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Objective:To explore the mechanism of Banxia Xiexintang （BXXX） in preventing and treating chronic atrophic gastritis （CAG） through Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway. Method:SD rats were divided into a normal group （<italic>n</italic>=12） and an experimental group for CAG model induction. The model rats were then randomly divided into a model group， a vatacoenayme （VG） group （60 mg·kg<sup>-1</sup>）， and high- （280 mg·kg<sup>-1</sup>）， medium- （140 mg·kg<sup>-1</sup>）， and low-dose （70 mg·kg<sup>-1</sup>） BXXX groups. The doses in the BXXX groups were equivalent to 28， 14， and 7 g·kg<sup>-1</sup> crude drugs. The rats in the normal group and the model group received distilled water at an equal volume， and those in the VG group and the BXXX groups were treated correspondingly by gavage. After 12 weeks of treatment， hematoxylin-eosin （HE） staining was carried out to observe pathological changes in the gastric mucosa of CAG rats. Western blot and real-time fluorescence-based quantitative PCR was used to detect the protein and mRNA expression levels of Nrf2， glutathione S-transferase （GST）， and NAD （P）H：quinone oxidoreductase 1 （NQO1） in the gastric mucosa of CAG rats. Result:Compared with the normal group， the model group showed increased protein and mRNA expression levels of Nrf2， NQO1， and GST in the gastric mucosa of the rats （<italic>P</italic><0.05）， atrophic gastric mucosa， and even intestinal metaplasia. The protein and mRNA expression levels of Nrf2， NQO1， and GST in the VG group and the high- and medium-dose BXXX groups were lower than those in the model group （<italic>P</italic><0.05）， and gastric mucosa atrophy and intestinal metaplasia were significantly improved， especially in the high-dose BXXX group. However， the effect in the low-dose BXXX group was not significant. Conclusion:BXXX can blunt the transcriptional activity of Nrf2， shut down Nrf2 signaling pathway， and reduce the expression levels of NQO1 and GST to achieve normal oxidation-anti-oxidation balance， which may be one of its action mechanisms in the treatment of CAG.
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Objective:To explore the effects of Ginkgo biloba on regulating NF-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway in liver injury induced by coal-burning-borne endemic arsenic poisoning in rats.Methods:Group design method was adopted, according to body weight (80-100 g), a total of 30 Wistar rats were divided into 5 groups (6 rats in each group, half males and half females) by random number table method. The normal control group was fed with normal diet ad libitum for 4.5 months; the Ginkgo biloba control group was fed with Ginkgo biloba (25 mg/kg, 6 d/week) for 1.5 months after normal feeding for 3 months; the drinking water arsenic poisoning group and the arsenic contaminated grain group were fed respectively with 100 mg/L arsenic trioxide (As 2O 3) solution and 100 mg/kg arsenic-containing feed for 3 months, and then fed with normal diet for 1.5 months; the Ginkgo biloba treatment group was fed with 100 mg/kg arsenic-containing feed for 3 months, and then was given Ginkgo biloba (25 mg/kg, 6 d/week) for 1.5 months. After sacrificing the animals, the content of malondialdehyde (MDA), the activity of copper zinc superoxide dismutase (SOD1) and the activity of glutathione peroxidase (GPx) in serum were detected by thiobarbituric acid colorimetry, xanthine oxidase method and dimercaptodinitrobenzoic acid reduction method, respectively. The mRNA and protein expressions of indicator genes of Nrf2-Keap1-ARE signaling pathway in liver tissues were detected by quantitative real-time PCR, immunohistochemistry and Western blotting. Correlation between the indexes was analyzed by Pearson. Results:In drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group, the contents of MDA in serum were (3.54±0.51), (3.83±0.87) and (2.93±0.84) μmol/L, respectively, which were higher than that in normal control group [(1.85±0.36) μmol/L, P < 0.05]; and SOD1 activities [(68.21±4.37), (64.53±9.96), (73.09±5.43) U/ml] and GPx activities [(486.41±40.45), (458.24±42.25), (539.79±79.43) U/L] in serum were lower than those in normal control group [(81.47±5.73) U/ml, (747.86±80.33) U/L, P < 0.05]. Compared with the arsenic contaminated grain group, the content of MDA in serum in Ginkgo biloba treatment group was decreased, the activities of SOD1 and GPx in serum were increased ( P < 0.05). Compared with normal control group, the mRNA expressions of SOD1 and GPx1 in the liver tissues in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group were significantly higher ( P < 0.05). Compared with arsenic contaminated grain group, the mRNA expressions of SOD1 and GPx1 in the liver tissue in Ginkgo biloba treatment group were increased ( P < 0.05). Compared with the normal control group, the protein expression of SOD1 in liver tissue in arsenic contaminated grain group was decreased ( P < 0.05), the protein expressions of GPx1 were decreased in the liver tissues in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expressions of SOD1 and GPx1 were increased in the liver tissue in Ginkgo biloba treatment group ( P < 0.05). Compared with the normal control group and arsenic contaminated grain group, the protein expression of Keap1 was decreased in the liver tissue in Ginkgo biloba treatment group ( P < 0.05). Compared with the normal control group, the protein expressions of Nrf2 and phosphorylation of Nrf2 (pNrf2) were increased in the cytoplasm in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expression of pNrf2 was decreased in the cytoplasm in Ginkgo biloba treatment group ( P < 0.05). The protein expressions of Nrf2 and pNrf2 in the nucleus in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group were also higher than those in normal control group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expressions of Nrf2 and pNrf2 were increased in the nucleus in Ginkgo biloba treatment group ( P < 0.05). The results of correlation analysis revealed that the protein expressions of Nrf2 and pNrf2 in the nucleus were negatively correlated with Keap1 protein expression ( r=-0.523,-0.401, P < 0.05), and positively correlated with the mRNA expressions of SOD1 and GPx1 ( r=0.658, 0.530, 0.555, 0.603, P < 0.05). In addition, the protein expressions of SOD1 and GPx1 were positively correlated with their enzyme activities ( r=0.472, 0.629, P < 0.05). Conclusions:Arsenic could induce oxidative stress and liver injury. Ginkgo biloba could reduce the protein expression of Keap1, and promote nuclear translocation of Nrf2, which might induce the up-regulation of mRNA expressions of SOD1 and GPx1, and partially reverse the posttranscriptional regulation of arsenic on SOD1 and GPx1, and then increase their protein expressions and enzyme activities, thereby improve arsenic induced oxidative stress and liver injury.
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Multiple sclerosis (MS) is a chronic inflammatory disease, mainly due to the activation of the T cells, which makes oxidative stress reaction in brain and leads to demyelination finally. Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor-2 (Nrf2)/antioxidant responsive element (ARE) signal pathway is one of the most important endogenous antioxidant pathways, which promotes the expression of detoxification enzymes and antioxidant protein to eliminate oxygen free radicals and balance intracellular redox system. Activation of the Keap1-Nrf2/ARE may delay the progression of MS by drugs or rehabilitation.
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Abstract Purpose: To investigate the influence of lycium barbarum polysaccharides (LBP), a functional derivative from lycium barbarum, on septic kidney injury. Methods: The SD male rats were randomly divided into 8 groups. The concentration of IL-1β, IL-6, IL-8, TNF-α, NF-κB and ROS, in kidney cortex homogenates after 12 h treatments were determined by enzyme-linked immunosorbent assay and ROS test kit, respectively. Morphology observation of kidney tissue was conducted with HE staining. The mRNA and protein expression levels of Nrf2, HO-1, NQO1, NF-κB, and Keap1 in kidney tissues were determined by qRT-PCR and Western blot, respectively. Results: LPS treatment significantly increased the oxidative stress. After LBP treatment, the ROS content reduced significantly in a dose-depend manner. However, the levels of HO-1, NQO1 and Nrf2 as molecular elements that respond to oxidative stress were further increased. Also, administration of LBP increased the levels of NF-κB and Keap1, and decreased the levels of Nrf2 in the Keap 1-Nrf2∕ARE signaling pathway. By administrating the brusatol, the inhibition of Nrf2 enhanced the expression of NF-κB, inhibits the antioxidant responses, and further reverse the protective effect of LBP on the LPS induced septic kidney injury. Conclusion: Lycium barbarum polysaccharides can reduce inflammation and activate the antioxidant responses via regulating the level of pro-inflammatory cytokines and the Keap1-Nrf2/ARE signaling pathway.
Subject(s)
Animals , Male , Rats , Drugs, Chinese Herbal/therapeutic use , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Signal Transduction/drug effects , Cytokines/drug effects , Disease Models, AnimalABSTRACT
Objective To investigate the role of UDP-glucuronosyltransferase 1A (UGT1A),nuclear factor erythroid-2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 ( Keapl ) in the tumorigenesis of colonic carcinoma.Methods The expressions of UGT1 A,Nrf2 and Keapl were detected in normal colonic mucosa(24 cases),adenoma tissue (30 cases) and adenocarcinoma tissue (77 cases) by immunohistochemistry,and the relationship between their expressions and the clinical pathological characteristics was analyzed.Results The positive rates of UGT1 A in normal colonic mucosa,adenoma and adenocarcinoma tissue were 83.3％ ( 20/24),80.0％ ( 24/30 ) and 53.2％ ( 41/77 ),respectively.The positive rate of UGT1A in adenocarcinoma was lower than those in colonic mucosa and adenoma ( all P ＜0.05 ).On the contrary,the positive rates of Nrf2 in adenoma [70.0％ (21/30) ] and adenocarcinoma tissue [ 87.0％ (67/77) ] were higher than that in normal colonic tissue [ 41.7％ (10/24),all P =0.000 ].The positive rates of Keapl in normal colonic mucosa,adenoma and adenocarcinoma tissue were 54.2％ ( 13/24),70.0％ (21/30) and 61.0％ (47/77),respectively ( normal colonic tissue vs adenocarcinoma tissue,P =0.040 ; adenoma vs adenocarcinoma,P =0.002 ).There was no correlation between the expression of UGT1 A,Nrf2 and the clinicopathologic features of colon carcinoma,while the differences of Keapl positive rates in the various degrees of tumor differentiation [ moderately-well differentiated vs poorly differentiated:70.0％ (35/50) vs 44.4％ (12/27) ] and invasion [T1-T2 vs T3-T4:78.8％ (26/33) vs 47.7％ (21/44) ]were statistically significant (all P ＜ 0.05 ).Conclusion The decreased expression of UGT1A and the dysregulation of Nrf2/Keapl system may play a role in colonic tumorigenesis.