Irisin inhibits myocardial injury induced by cobalt dichloride through regulating Sirtl/UCP2 pathway / 中国药理学通报

Aim To investigate the role and specific mechanisms of muscle factor Irisin in regulating the intracellular protective protein Sirtl and mitochondrial uncoupling protein 2 (UCP2) during myocardial hypoxia. Methods H9c2 cells were treated with CoC12 for 24 hours to construct an in vitro hypoxia model of myocardial cells. Six groups were divided in this experiment; control group (control), Irisin group (10 nmol • L

Myocardial specific overexpression of Sirt1 inhibits recovery of cardiac function in mice with myocardial ischemia / 中国药理学通报

Aim To investigate the effect of overexpression of silent information regulator 1 (Sirtl) on cardiac function in mice with myocardial ischemia. Methods Myocardial specific Sirtl overexpression transgenic mice (Sirtl-Tg) and littermate control mice (C57BL/6J), half male and half female, were randomly divided into control sham operation group (Con), control model group (Con +ISO), Sirtl overexpression sham operation group (Sirtl-Tg) and Sirtl overexpression model group (Sirtl-Tg + ISO). Isoproterenol (ISO) was injected subcutaneously into the back of the neck at 100 mg • kg

Intervention of total saponins of Panax japonicas on non-alcoholic steatohepatitis in mice by regulating miR-199/SIRTl/MFN2 / 中国药理学通报

Aim To discuss the effect of miR-199/ SIRT1/MFN2 signaling pathway on the progression of NASH and its related mechanisms.Methods 45 BALB/e mice were randomly divided into normal group, high fat diet(HFD) group, total saponins of panax japonicas ( TSPJ ) low-dose group ( 15 mg • kg-1) and TSPJ high-dose group (45 mg • kg"1 ).Normal group was given normal diet, while HFD group, TSPJ low-dose and high-dose groups were given high-fat diet.The mice were intragastrioally given 15 and 45 mg 'kg"1 TSPJ (dissolved in saline) daily in TSPJ low-dose and high-dose groups, while those in other groups were intragastric ally given the same a- mount of saline daily.After seven months, they were sacrificed for serum collection and hepatic tissue col¬lection.Results HE staining showed that liver lipido¬sis and inflammation were obvious in HFD group.while liver lipidosis anrl inflammation were alleviated in TSPJ group.MFN2 and SIRT1 levels significantly de¬creased.TNF-a, 1L-1 p , SREBP, ChREBP levels sig¬nificantly increased in HFD group.After treated with TSPJ, SIRT1 and MFN2 levels were significantly up- regulated , while TNF-a, IL-ip, ChREBP and SREBP levels were significantly down-regulated.The Immuno¬fluorescence results showed that the fluorescence inten¬sity of MFN2 and SIR 11 increased in TSPJ low-dose and high-dose groups.At mRNA level, miR-199 had a negative regulatory relationship with SIRT1.Conclu¬sions TSPJ can alleviate NASH induced by high fat diet through miR-199/SIRTl/MFN2 signaling path¬way.

Resveratrol inhibits progression of IgA nephropathy in rats by inhibiting proliferation of mesangial cells and down regulating expression of PDGF-B and TGF-β1 / 中国药理学通报

Aim To investigate the therapeutic effect of SirTl agonist resveratrol on IgA nephropathy rats and its mechanisms. Methods An IgA nephropathy rat model was established. The rats were divided into four groups randomly: control group, IgA nephropathy group, control treated with Res group and IgA nephropathy treated with Res group. The urine protein was detected by Ponceau S; the biochemical indexes were detected by automatic biochemical analyzer; the pathological changes of kidney were observed by PAS and Masson staining; IgA deposition was observed by immunofluorescence; the expressions of PDGF-B and TGF-fil were detected by immunohistochemistry. Results Compared with IgA nephropathy group, the volume of 24-hour urinary protein and the expression of BUN and Scr in Res group decreased significantly, and the fluorescence of IgA in glomerulus was less in resveratrol group; mesangial cells and matrix proliferated and glomerular volume increased in IgA nephropathy group at the later stage, and both of them were significantly inhibited. Resveratrol could significantly reduce the high expression of PDGF-B and TGF-β1 in IgA nephropathy group. Conclusions Res can inhibit the deposition of IgA immune complex in mesangial region of IgA nephropathy rats and reduce glomerulosclerosis by down-regulating the expression of PDGF-B and TGF-β1, in turn it suppresses cell proliferation in mesangial region. It suggests that resveratrol plays an important role in slowing down the progression of IgA nephropathy.

The protective effects of sevoflurane postconditioning mediated by SIRTl on learning and memory impairment in liemorrhagic shock and resuscitation mice / 中国药理学通报

Aim To explore the role of the silent information regulator (silent information regulation 1, SIRTl)-mediated apoptotic pathway in the protection of sevoflurane postconditioning in hippocampal neuronal injury of mice induced by hemorrhagic shock resuscitation (HSR). Methods A mouse model of HSR was established. The male C57BL/6J mice were randomly divided into; sham operation group (Sham group), HSR group (Shock group), sevoflurane treatment group (Sevo group), sevoflurane combined with SIRTl specific inhibitor treatment group (EX527 + Sevo group) and EX527 treatment group (EX527 group). The volume of cerebral infarction was detected by TTC staining method. The changes of hippocampal nerve cells in each group of mice were detected by TUNEL staining method. The learning and memory abilities were detected by Morris water maze test. The expression of SIRTl and apoptosis-related protein levels were delected by Western blot analysis. Results The latency of the model mice reaching the platform in Morris water maze test was prolonged, while the movement distance in the target quadrant was similarly reduced. Besides, the cerebral infarction volume remarkably increased. The number of TUNEL staining positive cells increased, and the expression of SIRTl and Bel-2 decreased while the pro-apoptosis protein Bax, and cleaved-caspase 3 expression level increased; sevoflurane treatment improved nerve injury in HSR. After combined treatment with sevoflurane and SIRTl inhibitor EX527, the protective effect of sevoflurane was attenuated on nerve injury in HSR. Conclusion Sevoflurane may play a protective role against hippocampal neuronal injury caused by HSR mediated by SIRTl apoptosis-related pathway.

Melatonin receptor agonist neu-pll improves insulin resistance in T2DM rats / 中国药理学通报

Aim To study the effect of melatonin receptor agonist Neu-pl 1 on IR in T2DM rats and to predict its possible mechanism. Methods Long-term high-fat feeding plus low-dose streptozotocin (STZ, 30 mg • kg"1, IP) were used to induce an animal model of type 2 diabetes in female rats. After 4 weeks of intragastric administration, liver tissue was sacrificed. Hie mRNA expression levels of Sirtl, Nrf-1/2 and ERRa in rats were determined by RT-PCR. The relative expressions of PGC-la and Mfn2 were determined by Western blot. Rat INS was measured and HOME-IR and ISI were calculated. The liver ATP content and ATPase activity were measured. Results Compared with normal group, T2DM rats developed IR, PGC-la, Mfn2 protein expression increased, Sirtl and other mRNA expression decreased significantly, ERRa mRNA expression increased, ATP content decreased significantly, and ATPase activity decreased. Compared with model group, the Neu-pll low-dose group reduced INS in T2DM rats, improved IR in T2DM rats, up-regulated rat liver protein and mRNA expression, down-regulated ERRa mRNA expression, and increased rat liver ATP content and ATPase activity. Conclusions The melatonin receptor agonist Neu-pl 1 may improve IR by regulating the mitochondrial bal-ance-related factors in liver of T2DM rats and maintaining normal mitochondrial function.

Dihydromyricetin promoted browning of subscapular adipose tissues in obese mice fed with high-fat diet via activating AMPK-PGC1 a-Sirtl signaling pathway / 中国药理学通报

Aim To observe the effect of dihydromyricetin (DHM) on the browning of subscapular adipose tissues in the high-fat diet fed obese mice, and clarify the mechanism. Methods C57BL/6J mice were fed with normal and high-fat diet, and were treated with or without low dose (125 mg • kg"1 • d"1) or high dose (250 mg • kg"1 • d"1) DHM for 16W. The body mass of mice was measured every four weeks during the experiment. After 16 weeks, the mice were fasted overnight. Blood samples were taken for fasting blood glucose. The mice were then sacrificed and the body length measured. The Lee' s index was calculated. The size of the subscapular adipocytes was observed by HE staining. The mRNA and protein expression of uncoupling protein 1 (UCP1) , PR domain containing 16 (Prdml6) , adenylate-activated protein kinase (AMPK) , peroxisome proliferator-activated receptor gamma-assisted activator alpha (PGCla) and silencing signal regulator 1 (Sirtl) were assessed by real time quantitative PCR and Western blot assay. Results Compared with normal control group (ND group) , the body mass of mice in high-fat diet group (HFD group) significantly increased, suggesting that the obese mice model was successfully replicated. In addition , blood glucose, Lee' s index and the fat cell diameter of the subscapular adipose tissues in HFD group all significantly increased, while the mRNA and pro-tein expression of UCP1, Prdml6, AMPK, PGCla and Sirtl significantly decreased. DHM markedly re-versed the changes of the above indexes of HFD mice, but DHM did not significantly affect the above indexes of normal mice. Conclusions Dihydromyricetin promotes the browning of subscapular adipose tissues in mice fed with high-fat diet, which might be via activating AMPK-PGC1 a-Sirtl signaling pathway.