ABSTRACT
AIM:To observe the effect of Tangshenfang(TS)on the liver protection and the levels of silent in-formation regulator 1(SIRT1)and peroxisom proliferator-activated receptor γcoactivator-1α(PGC-1α)in the liver tissue. METHODS:The rat model of diabetes mellitus(DM)was established by intravenous injection of streptozotocin(STZ;30 mg/kg)after having the high fat/high glucose diets for 1 month.The diabetic rats were randomly divided into DM group,DM with high-dose TS(TSHi)group, medium-dose TS(TSMed)group and low-dose TS(TSLow)group.The normal rats were served as control group.There were 8 rats in each group.After treatment with TS for 12 weeks,the serum biochemical indi-ces including fasting blood glucose(FBG), triglyceride(TG), alanine aminotransferase(ALT)and aspartate aminotrans-ferase(AST)were tested.Fasting insulin(FINS)was also detected by radioimmunoassay,and homeostatic model assess-ment for insulin resistance(HOMA-IR)was calculated.The serum levels of tumor necrosis factor-α(TNF-α)and interleu-kin-1(IL-1)were measured by ELISA.The activity of SOD and content of MDA in the liver tissues were measured by the methods of hydroxylamine and thiobarbituric acid.The liver pathological changes were observed under light microscope with HE and Masson staining.The protein expression of SIRT1and PGC-1αin the liver tissues was determined by Western blot. RESULTS:In DM group,serum FBG,TG,ALT,AST,FINS,HOMA-IR,TNF-αand IL-1 were obviously increased com-pared with the control group(P<0.01).The fatty changes,local necrosis,inflammation and fibrosis in the liver tissues were observed.The content of MDA in liver increased,while the activity of SOD decreased markedly.The protein expression of SIRT1 and PGC-1αwas decreased(P<0.05).In TS treatment groups,all these changes in DM rats were markedly reversed by TS,and the protein expression of SIRT1 and PGC-1αin the liver tissues was markedly increased.CONCLUSION:TS may protect the rats from diabetic liver injury by increasing the expression of SIRT 1 and PGC-1α,and thereby improving in-sulin resistance and oxidative stress.
ABSTRACT
To observe the effect and mechanism of Yiqi Tongluo Jiedu capsule aganist cerebral ischemia reperfusion injury, the SD rats were randomly divided into following groups: sham-operated group, model group, the group of low, medium and high dose of Yiqi Tongluo Jiedu capsule, and nimodipine group. Using focal middle cerebral artery embolization (MCAO) model, following items were observed: symptoms of neurological deficit score; infarct volume; activity of SOD, content of MDA and NO, activity of NOS of ischemic brain tissue; Bcl-2 and Bax protein expression; content of IL-1beta, IL-6 and TNFalpha in serum; IL-1beta mRNA expression of ischemic brain tissue. Results showed that Yiqi Tongluo Jiedu capsule could significantly reduce the symptoms of neurological deficits, promote the recovery symptoms of neurological deficits; narrow infarct volume of brain tissue obviously, reduce the percentage of infarct volume; raise activity of SOD, reduce content of MDA and NO, reduce activity of NOS; increase Bcl-2 protein, reduce Bax expression; reduce content of IL-1beta, IL-6 and TNFa in serum; reduce IL-1beta mRNA expression of ischemic brain tissue. Yiqi Tongluo Jiedu capsule has significant protective effects against ischemic brain injury, it has significant anti-apoptotic, antioxidant and anti-inflammatory effects.
Subject(s)
Animals , Male , Rats , Brain , Metabolism , Pathology , Capsules , Drugs, Chinese Herbal , Pharmacology , Infarction, Middle Cerebral Artery , Pathology , Interleukin-1beta , Blood , Genetics , Interleukin-6 , Blood , Malondialdehyde , Metabolism , Nitric Oxide , Metabolism , Nitric Oxide Synthase , Metabolism , Plants, Medicinal , Chemistry , Proto-Oncogene Proteins c-bcl-2 , Metabolism , RNA, Messenger , Metabolism , Random Allocation , Rats, Sprague-Dawley , Reperfusion Injury , Blood , Metabolism , Pathology , Superoxide Dismutase , Metabolism , Tumor Necrosis Factor-alpha , Blood , bcl-2-Associated X Protein , MetabolismABSTRACT
The aim of the present study is to investigate the role of nordihydroguaiaretic acid (NDGA) on inflammatory cells accumulation after focal cerebral ischemia and the underlying mechanism. Focal cerebral ischemia was induced by 30 min of middle cerebral artery occlusion (MCAO) followed by 72 h of reperfusion. NDGA (5 and 10 mg/kg) was administered intraperitoneally 30 min, 2, 24, 48 h after reperfusion, respectively. The brain injuries were observed by neurological and histological examination. Endogenous IgG exudation, neutrophils and macrophages/microglia accumulation, and intercellular adhesion molecule-1 (ICAM-1) protein expression were determined by immunohistochemistry 72 h after reperfusion. ICAM-1 mRNA was determined by RT-PCR 72 h after reperfusion. The catalysates of 5-lipoxygenase (5-LOX), leukotriene B4 (LTB4) and cysteinyl leukotrienes (CysLTs), were evaluated by ELISA 3 h after reperfusion. The results showed that NDGA ameliorated neurological dysfunction, decreased infarct volume, and inhibited endogenous IgG exudation, neutrophils infiltration, ICAM-1 mRNA and protein expression 72 h after reperfusion. Moreover, NDGA reduced the levels of LTB4 and CysLTs 3 h after reperfusion. However, NDGA did not reduce the accumulation of macrophages/microglia 72 h after reperfusion. These results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.
Subject(s)
Animals , Male , Rats , Arachidonate 5-Lipoxygenase , Metabolism , Brain Ischemia , Immunoglobulin G , Allergy and Immunology , Inflammation , Intercellular Adhesion Molecule-1 , Genetics , Metabolism , Leukotriene B4 , Metabolism , Lipoxygenase Inhibitors , Pharmacology , Masoprocol , Pharmacology , Neutrophils , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Reperfusion InjuryABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of Angiotensin (ANG)-(1-7) on postangioplasty fibrotic remodeling and the involvement of TGF-beta/Smad signaling pathway in this process.</p><p><b>METHODS</b>Thirty two healthy New Zealand white rabbits were randomly divided into 4 groups: sham group, control group, ANG-(1-7) group and ANG-(1-7) + A-779 group. Rabbits underwent angioplasty in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was implanted for saline, ANG-(1-7) (576 microg x kg(-1) x d(-1)) or ANG-(1-7) + A-779 (576 microg x kg(-1) x d(-1)) delivery. Before and after 4 weeks treatment, the levels of ANG II in plasma were measured by ELISA. At week 4, angiography and histomorphometric analysis were performed, mRNA levels of collagen I and III were assayed by RT-PCR and protein levels of TGF-beta1 and Smad2 in local vessel were assayed by Western blot.</p><p><b>RESULTS</b>Following 4 weeks treatment, ANG-(1-7) and ANG-(1-7) + A-779 group displayed a significant elevation in lumen diameter [(4.11 +/- 0.10) mm and (3.34 +/- 0.11) mm vs. (2.88 +/- 0.08) mm, P < 0.05, respectively] and reduction in neointimal thickness [(208 +/- 17) microm and (407 +/- 25) microm vs. (448 +/- 15) microm, P < 0.05, respectively], neointimal area [(0.27 +/- 0.09) mm2 and (0.38 +/- 0.01) mm2 vs. (0.41 +/- 0.02) mm2, P < 0.05, respectively] and restenosis rate [(28.1 +/- 2.7)% and (36.8 +/- 2.2)% vs. (40.1 +/- 2.7)%, P < 0.05, respectively] compared with control group. Collagen I, III mRNA and TGF-beta1, Smad2 protein levels were significantly elevated in control group, ANG-(1-7) group and ANG-(1-7) +A-779 group compared to sham group (P < 0.01 or P < 0.05) and reduced in ANG-(1-7) group compared to control group (all P < 0.05). Co-treatment with A-779 reversed the inhibitory action of ANG-(1-7). Plasma levels of ANG II postangioplasty were similar in control and ANG-(1-7) group and both were significantly higher than preoperation levels.</p><p><b>CONCLUSION</b>ANG-(1-7) attenuates postangioplasty collagen synthesis in rabbits possibly through down-regulating the expression of TGF-beta1 and inhibiting the activation of Smad2 pathway.</p>