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Objective To study the effects of exogenous hydrogen sulfide (H2S) on myocardial fibrosis of diabetic mice and the mechanism thereof. Methods Twenty-four male adult C57BL/6J mice were randomly divided into 4 groups (6 each): normal control group (NC group), diabetes mellitus group (ALX group), diabetes mellitus treated with low dose NaHS group (ALX+LDNaHS group) and diabetes mellitus treated with high dose NaHS group (ALX+HDNaHS group). The diabetic mouse model was established by intraperitoneal injection of alloxan at 200mg/kg. Mice in NC group and ALX group drank tap water freely everyday, and in ALX+LDNaHS group and ALX+HDNaHS group were provided with sodium hydrosulfide (NaHS, donor of H2S, 30μmol/L and 90μmol/L, respectively) in drinking water, and the histological specimens of mice were examined 8 weeks later. The morphological changes of cardiac tissue were examined with HE staining. The expressions of mRNA of p38mitogen-activated protein kinase (p38MAPK) and nuclear transcription factor kappa B p65 (NF-κB p65) were detected by Real-time PCR, and the expressions of p-p38MAPK, p-NF-κB p65 and Collagen I proteins were detected by Western blotting. Results Compared with NC group, the expression of collagen increased and there was fibrillation in the myocardial matrix, the expressions of mRNA of p38MAPK and NF-κB p65 increased obviously (P<0.01), the protein expressions of p-p38MAPK, p-NF-κB p65 and Collagen I increased significantly (P<0.01) in ALX group; after intervention of H2S, the cardiac muscle fibers were parallel arranged, the expression of collagen was visibly decreased and there was less fibrillation in the myocardial matrix, the expressions of mRNA of p38MAPK and NF-κB p65 were obviously decreased (P<0.01), the protein expressions of p-p38MAPK, p-NF-κB p65 and Collagen I were significantly decreased (P<0.01), and more improvement was observed in ALX+HDNAHS group than in ALX+LDNAHS group (P<0.05). Conclusion H2S can ameliorate myocardial fibrosis in diabetic mice, which might be related to the regulation of p38MAPK and NF-κB p65-mediated inflammatory reaction.
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Background:Hepatic veno-occlusive disease( HVOD) is a disease characterized by hepatomegaly,jaundice, ascites,weight gain and lack of effective treatment currently. Our prophase research showed that ligustrazine had therapeutic effect on Sedum aizoon induced HVOD in mice. Aims:To investigate the mechanism of therapeutic effect of ligustrazine on Sedum aizoon induced HVOD in mice. Methods:A total of 115 mice were randomly divided into 4 groups:mice in group A were intragastrically administrated with 30 mg·kg-1 ·d-1 Sedum aizoon to induce HVOD and served as model group;mice in group B were given 30 mg·kg-1 ·d-1 Sedum aizoon + 100 mg·kg-1 ·d-1 ligustrazine and served as low dose ligustrazine intervention group;mice in group C were given 30 mg·kg-1 ·d-1 Sedum aizoon + 200 mg·kg-1 ·d-1 ligustrazine and served as high dose ligustrazine intervention group;mice in group D were given 30 mg·kg-1 ·d-1 PBS and served as normal control group. After 30 days,all the mice were sacrificed. HE staining and Masson staining were performed for histological examination. The mRNA and protein expressions of tissue factor(TF),nuclear factor(NF)-κBp65 and early growth response factor( Egr)-1 in liver tissue were determined by RT-PCR and Western blotting, respectively. Results:HE staining and Masson staining histological examination showed that ligustrazine could obviously ameliorate the pathological injury of liver tissue in HVOD mice. Compared with group D,the mRNA and protein expressions of TF,NF-κBp65,Egr-1 were significantly increased in group A( P 0. 05). Conclusions:Ligustrazine has therapeutic effect on HVOD,the possible mechanism is that ligustrazine could interrupt the activation of coagulation system by reducing the expression of TF via down regulating the expressions of NF-κBp65 and Egr-1,especially in high dose ligustrazine group.
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Objective To investigate the effects of HMG-CoA reductase inhibitor rosuvastatin on atherosclerosis and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and nuclear factor (NF)-kB p65 expressions in apolipoprotein E (ApoE)-deficient mice. Methods Twenty six-week-old ApoE-deficient male mice were randomly divided into hyperlipidemia model group (n=10) and rosuvastatin group (n=10), and they were fed high-fat diet for 13 weeks. Ten six-week-old C57BL/6J (wild type, WT) male mice were selected as normal control group, and were fed normal diet for 13 weeks. After 13 weeks, blood was drawn from the mice to determine serum levels of total cholesterol (TCH), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C). These mice were sacrificed, and their aortas were obtained and examined with HE staining; Western blotting and RT-PCR were used to analyze LOX-1, NF-kB p65 expression intensity in aorta tissue quantitatively. Results The serum level of TCH, TG and LDL-C in rosuvastatin group were lower than those in hyperlipidemia model group (P<0.05). Pathological observation showed that atherosclerotic lesions of the aortas were aggravated significantly in hyperlipidemia model group but alleviated in rosuvastatin group compared with normal control group. Compared with normal control group, LOX-1, NF-kB p65 protein and mRNA expressions significantly increased in hyperlipidemia model group (P<0.05) and reduced in rosuvastatin group (P<0.05). Conclusions Rosuvastatin may lower blood lipid significantly, alleviate the degree of atherosclerotic lesions, and inhibit LOX-1, NF-kB p65 protein and mRNA expressions in the aortic tissue of ApoE-deficient mice. Its anti-athrosclerosis effect is related to down regulation of LOX-1 and NF-kB p65 expressions.
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BACKGROUND/AIMS: Nuclear factor-kappa B p65 (NF-kappa B p65), nuclear factor-kappa B1 p50 (NF-kappa B p50) have been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated protein kinase (MAPK)/ NF-kappa B/ cyclin D1 signaling pathway has been shown to play an important part in the pathogenesis of human cancers. This study was designed to investigate the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal adenocarcinoma. METHODS: Paraffin sections of 20 normal mucosa, 20 low-grade tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were analysed immunohistochemically for the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins. RESULTS: The expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins were significantly higher in adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappa B p50 was more frequent in poorly differentiated histologic grade, presence of nodal metastasis, and advanced stage. Expression of p38 MAPK alpha protein was higher in advanced tumor stage, presence of nodal metastasis and advanced stage. Synchronous expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins were significantly higher in adenocarcinoma tissue. CONCULSIONS: With the increased expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins, p38 MAPK/ NF-kappa B/ cyclin D1 signaling pathway may play a role in the pathogenesis of colorectal carcinoma.
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Female , Humans , Male , Middle Aged , Adenocarcinoma/enzymology , Colorectal Neoplasms/enzymology , Cyclin D1/immunology , Data Interpretation, Statistical , Immunohistochemistry , Intestinal Mucosa/metabolism , NF-kappa B/immunology , NF-kappa B p50 Subunit/immunology , Neoplasm Staging , Precancerous Conditions/enzymology , Transcription Factor RelA/immunology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Objective To explore the expression of PTEN,NF-KB p65 and Survivin protein and the influence in the genesis and development of endometrial carcinoma(EC).Methods The expression of PTEN.NF-KB and Survivin in 63 cases of EC and 20 cases normal endometrial tissue specimens were detected by immunohistochemistry.Resuits There were obvious differences among the positive rates of PTEN.N-KB p65 and Survivin protein in EC compared with in normal endometrial tissue specimens (P＜0.001).The clinicopathological characteristics of endometrial carcinoma with PTEN,NF-KB p65 and Survivin were as follows:the expression of PTEN gene was positively correlated with the degree of histological differentiation(P＜0.001),and it was negatively correlated with lymph node metastasis and TNM (P＜0.005).There was inverse correlation between the expression of NF-KB p65 gene and the degree of histological differentiation(P＜0.05).It was positively correlated with lymph node metastasis,deep myometrial invasion and TNM in EC (P＜0.05).The expression of Survivin was positively correlated with the clinical stage and lymph node metastasis and deep myometrial invasion in EC(P＜0.05).Conclusion There are difierent extent action of PTEN.NF-KB p65 and Survivin significantly in genesis and development of EC.Detection of PrEN combined with NF-KB p65 and Survivin is valuable for early diagnosing and evaluating malignancy extent of EC.
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Objective To study the effect of simvastatin(SV) on NF-kappa B p65 expression in liver of insulin resistant rats. Methods Male Wistar rats were divided into two groups:basic chow(NC,n=15)or high-fat diet(HF,n=20)for 10 weeks feeding, then assessed by euglycemic-hyperinsulinemia clamp technique. Rats in HF group were treated with(HFS,n=5)and without (HFN,n=5) SV 10mgkg-1d-1 in gavage for 5 weeks.NF-kappa B p65 expressions were tested with Western blot. Results The glucose infusion rate (GIR) in HF group decreased significantly compared with NC group (P
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Objective:To investigate the expression and significance of NF-?B,and ICAM-1 in laryngeal carcinoma patients.Methods:Two groups of laryngeal carcinoma tissue (one group derived from the laryngeal carcinoma patients;the other from the normal persons) were detected for NF-kappa B P65 protein and ICAM-1′s expressions by immunohistochemistry staining.Results:(1)The expressions of NF-kappa B P65 protein and ICAM-1 of the laryngeal carcinoma patients were much more strengthened than those of the normal persons(P
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0.05) was observed. The protein expressions of TLR-4, NF-?B p65, HSP70 and ICAM-1mRNA in IR group were significantly increased as compared to C group and PD group, while those expressions in PD group were evidently higher than those in C group (all P