BACKGROUND: The restenosis occurs up to 20%-30% following metal coronary stent implantation. Under the support of the 863 program, the feasibility to treat coronary artery stenosis using a novel drug-eluting stent (DES) has been investigated to reduce restenosis. OBJECTIVE: A drug-eluting stent (rapamycin as drug mode) was implanted into porcine models of coronary stenosis. The safety and efficacy of the drug-eluting stent were observed and compared with bare-metal stent. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed in the Fu Wai Hospital for Cardiovascular Disease between November 2003 and April 2004. MATERIALS: A novel bioinspired phospholipid copolymer was synthesized by free radical polymerization of stearyl methacrylate, β-hydroxypropyl methacrylateand 3-(trimethoxysilyl) propylmethacrylate. METHODS: Twenty-one pigs were randomly divided into 3 groups: bare-mental stent, drug-eluting stent, and polymer-coated stent. The treated stents pre-loaded onto a delivery system through the use of crimping instrument were implanted into pig's coronary artery, with 2 stents per pig. MAIN OUTCOME MEASURES: Determination of luminal diameter, luminal area, mean intimal thickness on and between the stents, neointimal area, percentage of luminal area restenosis, and damage index using an image analysis instrument. RESULTS: At 28 days after implantation, there was significant difference in mean intimal thickness on and between the stents, as well as neointimal area, between the DES and bare-metal stent groups (P < 0.05). The neointimal area was reduced by 44.87% in the DES group compared with the bare-metal stent group. No significant difference in percentage of luminal area restenosis was found between the DES and bare-metal stent groups, but P value equaled to 0.053, which was close to 0.05. In addition, no restenosis was found in the DES group. CONCLUSION: Rapamycin DES can markedly resist intravascular intimal hyperplasia and restenosis following stenting.

A novel bioinspired phospholipid copolymer has been synthesized by the radical polymerization of poly2-Methacryloyloxyethylphosphorylcholine (MPC), stearyl methacrylate (SMA), hydroxypropyl methacrylate (HPMA) and trimethoxysilylpropyl methacrylate (TSMA). Contact angle results indicated that the coating surface rearranged to get a more hydrophilic surface at the polymer/water interface. The membrane mimic phosphorylcholine coating surface could resist the platelet adhesion and prolong plasma recalcification time significantly. Rapamycin was used as model drugs to prepare drug-eluting coating. The animal experiments showed that this novel drug-eluting stent could effectively prevent the phenomena of restenosis.
Angioplasty, Balloon, Coronary ; instrumentation ; Animals ; Coated Materials, Biocompatible ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Female ; Humans ; Male ; Materials Testing ; Methacrylates ; chemistry ; Phosphorylcholine ; analogs & derivatives ; chemistry ; Pilot Projects ; Polymers ; chemistry ; Prosthesis Design ; Random Allocation ; Sirolimus ; chemistry ; Swine ; Swine, Miniature

OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.

OBJECTIVE To investigate whether icari-in(ICA)plays a neuroprotective role by improving glyco-lytic function through activating Wnt/β-catenin signaling pathway.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish AD cell model,ICA was added in 2 h before Aβ25-35 and the DKK1(a specific inhibitor of the Wnt signaling pathway)was added in 0.5 h before ICA.Pharmacodynamic study:HT22 cells were divided into control group,ICA group(ICA 10 μmol·L-1),model group(Aβ25-3520 μmol·L-1),model + ICA group(Aβ25-3520 μmol·L-1 +ICA 2.5,5,10 μmol·L-1);Mechanism study:HT22 cells were divided into control group,model group,Aβ25-35+ICA 10 μmol·L-1 group,Aβ25-35+DKK1 group,Aβ25-35+DKK1+ ICA group.The cell viability was detected by MTT assay and the cell morphology was obtained by microscope,the lactate content was detected by lactate assay,the ATP content was measured with the chemiluminescence method,the expression levels of HK1,PKM1 and the pro-tein expression of molecules related to the Wnt/β-catenin signaling pathway(Wnt3a,GSK3β,pGSK3β Try216,pGSK3β Ser9,β-catenin,pβ-catenin Ser33/37 Thr41,Active β-catenin and nuclear β-catenin)was assayed by Western blotting.The nuclear translocation of β-catenin was observed by immunofluorescent staining.RESULTS Compared with the control group,the viability of cells in the model group was reduced,the morphology of cells was significantly damaged,the ATP content and lactate content were significantly decreased,and the glycolytic key enzymes:the protein levels of HK1,PKM1 and the protein levels of Wnt3a,pGSK3β Ser9,active β-catenin and nuclear β-catenin were significantly reduced,and the phosphorylation levels of β-catenin Ser33/37 Thr41 were significantly increased.Compared with the model group,the cell morphology was significantly improved and the viability was significantly increased,the ATP and lactate content were significantly increased,the expressions of HK1,PKM1 and Wnt3a,pGSK3β Ser9,active β-catenin and nuclear β-catenin protein were significantly upregulat-ed,and the phosphorylation levels of β-catenin Ser33/37 Thr41 were significantly reduced after ICA treatment.However,when the canonical Wnt signaling was inhibited by DKK1,the above effects of ICA on glycolysis were abolished.CONCLUSION ICA exerts neuroprotective effects on Aβ25-35-induced HT22 cell injury by enhancing the glycolysis function through the activation of the Wnt/β-catenin signaling pathway.