This study was aimed to explore whether gypenosides (GPs) can inhibit the expression of miRNA-122 and regulate the lipid metabolism enzyme activity to play a role in lipid-lowering effect. A total of 48 healthy male SD rats were randomly divided into 4 groups, which were the normal control group (C), hyperlipidemic model group (M), simvastatin group (S) and the GPs group (G). All groups were fed with high-fat diets except the normal control group which was fed with normal diets. The GPs, which were dissolved in 0.3% sodium carboxymethyl cellulose (CMC-Na) solution, were given by the intragastric administration. The C group and M group were given 0.3% CMC-Na solution (1 mL/100 g) daily. The G group was given 160 mg·kg-1 of GPs daily. The S group was given 5 mg·kg-1 of simvastatin daily. The experiment was continued for 8 weeks. After the last medication, rats were fasted for 12 hours. Rats were anesthetized with chloral hydrate (7%). Abdominal arterial blood samples were collected to detect the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). The wet weight of liver was weighed and the liver index was measured. The liver total RNA was extracted to determine the expression of miRNA-122 by the real-time PCR. The homogenates of liver tissues were prepared for the determination of hepatic lipase (HL), lipoprotein lipase (LPL) and HMG-CoA reductase activity. Cholesterol micelle formation experiments were implementedin vitro. The results showed that compared with the normal control group, TC, TG and LDL-C levels of the model group were significantly increased (P< 0.01), while the HDL-C levels in each group were obviously decreased (P< 0.05). Compared with the model group, TC, TG and LDL-C levels of the S group and G group were obviously decreased (P< 0.05), and the HDL-C level was obviously increased (P< 0.05). Compared with the model group, the liver indexes of the S group and G group were obviously decreased (P< 0.05). Compared with the hyperlipidemia model group, the expressions of miRNA-122 of the S group and G group were significantly reduced (P< 0.05). Compared with the hyperlipidemia model group, the activity of HMG-CoA reductase was obviously reduced in the S group and G group (P< 0.05), but the HL and LPL activities were obviously increased (P< 0.05). GPs can inhibit the formation of cholesterol micelles to some extent. It was concluded that GPs can effectively reduce the blood lipid level in hyperlipidemic rats, in order to relieve the hepatic fatty lesions. Its lipid-lowering mechanism was related to its inhibition of miRNA-122 expression and regulation of lipid metabolism enzyme activity, as well as the inhibition on the formation of cholesterol micelles.

Objective To explore the potential mechanism of curcumin(CUR) enhancing the sensitivity of acute myeloid leu-kemistem cells(LSCs) CD34+CD38-KG1cellto daunorubicin (DNR) .MethodThe expression of surface moleculeCD34 , CD38 in KG1cellwadetected by the flow cytometry .The half maximal inhibitory concentration (IC50 ) of curcumin to CD34+CD38-Kglcellwacalculated by the Mtmethod .MT,methylcellulose colony formation assay and flow cytometry were ap-plied to examine the effectof Dnon the proliferation ,clone forming ability and apoptosiin the two kindof cell(CD34+CD38-KG1celland CUR/CD34+CD38-KG1cells) respectively .The mRNA-expression of Bcl-2 ,Bax and XIAP in the two cellwere analyzed by RT-PC.Meanwhile ,the protein-expression of CyclinD1 ,Bcl-2 ,Bax and XIAP were detected by Western Blo.ResultThe percentage of CD34+CD38-KG1in KG1cell line wa(98 .2 ± 3 .2)% .The IC50 of curcumin treating CD34+CD38-KG1fo24 h wa100 μmol/L .The inhibition effecof high and middle concentration(0 .8 ,2 .0 μg/mL) of Dnon the proliferation of CUR/CD34+CD38-KG1cellwastrongethan thaof CD34+CD38-KG1cell(P＜0 .05) .The inhibitory role of Dnto the colony formation on CUR/CD34+CD38-KG1cellwamore effective than thaof CD34+ CD38-KG1cells(P＜0 .05) .The ap-optotirate of CUR/CD34+ CD38- KG1cellin each concentration group of Dnwahighethan thaof CD 34+ CD38- KG1cells(P＜0 .05) .The mRNA-expression of Bcl-2 and the protein-expression of Bcl-2 and CyclinD1 were down-regulated .Howeve, no significanchange waobserved aboth mRNA-expression and protein-expression of Bax and XIAP .Conclusion Cucan en-hance the sensitivity of CD34+CD38-KG1cellto DN,which mighbe associated with down-regulating the expression of Cy-clinD1and Bcl-2 .

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.