The in situ expression of PDGF-B mRNA increased after the denudation of rabbit iliac arteries

AIM: To elucidate the in vivo mechanisms of the proliferation of vascular smooth muscle cells (VSMCS) in injuried arteries. METHODS: A VSMCS proliferative model was constructed by injury of rabbit iliac arteries with balloon catheters and a probe designed for rabbit platelet-derived growth factor B chain (PDGF-B ) mRNA was used to detect the expression of it by intimal VSMCS on the vascular cross sections using an in situ hybridization technique at the indicated times. The relation of this expression to the proliferation of VSMCS by their expression of proliferating cell nuclear antigen (PCNA) and vascular intimal areas were estimated. RESULTS: The expression of PDGF-B mRNA of intimal VSMCS was increased when calculating the intimal PDGF-B mRNA positive cells per millimetre area at ×400 magnification with average numbers of 31.93±14.64 in 1 week group, 26.50±9.25 in 2 weeks group and 24.85±13.65 in 4 weeks group. This was in accordance with the expression of PCNA by VSMCS and the increase of intimal areas. CONCLUSION: The local production of PDGF-B by VSMCS via an autocrine mechanism is responsible for the continuous proliferation of these cells and formation of neointima after the injury. The probe designed is very useful for detecting rabbit PDGF-B mRNA.     

Phosphorothioate-modified antisense TGF-β1 oligodeoxynucleotide inhibits neointimal hyperplasia after vascular balloon injury in rats

AIM: To evaluate the effects of antisense TGF-β1 oligodeoxynucleotide (AS TGF-β1) on the expression of TGF-β1, deposition of extracellular matrix (ECM) and the neointima formation in the arteries after balloon injury. METHODS: The unmodified and phosphorothioate-modified AS TGF-β1 which containing 15 bases and surrounding the initiation codon region (ATG) of rat TGF-β1 complementary DNA (cDNA) were designed. At the same time, sense TGF-β1 oligodeoxynucleotide (S TGF-β1) with the base sequence complement to AS TGF-β1 was synthesized as a control. The oligodeoxynucleotides were introduced into in vivo and in vitro experiments, respectively. RESULTS: The AS TGF-β1 significantly inhibited the protein expression of TGF-β1 in a concentration-dependent manner, and S TGF-β1 did not have the same effect. Furthermore, no effect of the AS TGF-β1 on the mRNA expression of TGF-β1 in injured VSMCs was observed. Moreover, for the injured VSMCs, AS TGF-β1 significantly and concentration-dependently inhibited the basal DNA synthesis. Both AS TGF-β1 and S TGF-β1 did not exhibit dose-dependent effects on DNA synthesis in uninjured VSMCs. Fibronectin (FN) mRNA expression in injured VSMCs was significantly decreased by AS TGF-β1 in a concentration (001~1 μmol/L)-dependent manner. AS TGF-β1 significantly increased the mRNA expression of contractile marker SM22α, and decreased the mRNA expression of synthetic markers osteopontin and matrix Gla, especially at the concentration of 001 μmol/L and 01 μmol/L. After treatment with AS TGF-β1 (90 μg·kg-1·d-1) for 28 d, the neointima formation was significantly inhibited, and the area ratio of intima/media was markedly decreased by 68% compared with untreated group, but S TGF-β1 had no effect on neointimal formation. CONCLUSION：The AS TGF-β1 specifically inhibits the protein expression of TGF-β1 in the VSMCs derived from injured arteries. Moreover, it significantly inhibits DNA synthesis and cell proliferation, and decreases the expression of FN. Therefore, AS TGF-β1 dramatically attenuates neointima formation after balloon njury. The effects of AS TGF-β1 on the injured VSMCs may be associated with its reverse effects on the alteration of VSMC phenotype after balloon injury.     

Effect of parthenolide on neointimal hyperplasia after balloon injury

AIM: To detect the effect and underlying mechanism of parthenolide (PN) on neointimal hyperplasia. METHODS: After 1 week of high-fat feeding, 30 male New Zealand white rabbits (2.0~2.3 kg) were randomly divided into 6 groups: sham+NS, rabbits received 0.9% normal saline after sham operation; sham+DMSO, rabbits received DMSO after sham operation; balloon injury(BI)+NS, rabbits received NS after balloon injury; BI+DMSO, rabbits received DMSO after balloon injury; BI+PN low, rabbits received PN at 1 mg/kg after balloon injury; BI+PN high, rabbits received PN at 2 mg/kg after balloon injury. The drugs were intraperitoneal injected once a day after the operation until sacrifice. After fed with high-fat diet for 4 weeks, the intima-media thickness, the expression of caspase-1, IL-1β, the levels of IL-8, TC, TG, LDL and HDL in the serum were measured. RESULTS: Compared with sham+DMSO group, the thickness of intima, the amount of caspase-1, IL-1β and IL-8 in BI+DMSO group were significantly increased (P<0.05). The levels of caspase-1, IL-1β and IL-8 were significantly decreased in BI+PN high group compared with BI+DMSO group (P<0.05). CONCLUSION: Neointimal hyperplasia is suppressed by PN after balloon injury, the potential mechanism may be associated with its anti-inflammatory role.     

Effects of PDGFRα on melanocyte apoptosis induced by hydrogen peroxide

AIM: To investigate the effects of platelet-derived growth factor receptor α (PDGFRα) on melanocyte apoptosis induced by hydrogen peroxide (H₂O₂). METHODS: Melanocyte PIGI was used as the research object. After exposed to H₂O₂ at different concentrations, the cell viability was detected by MTT assay. The PIGI cells were transfec-ted with empty vector pCMV6 or PDGFRα over-expression vector pCMV6-PDGFRα. The transfection efficiency was determined by RT-qPCR and Western blot. The effect of H₂O₂ on the viability of the PIGI cells after over-expression of PDGFRα was measured by MTT assay. The cell apoptosis was analyzed by flow cytometry. The protein levels of p38, p-p38 and cleaved caspase-3 in the cells were detected by Western blot. DCDHF-DA was used to estemate the generation of reactive oxygen species (ROS) in the cells. RESULTS: The viability of PIGI cells decreased after exposed to H₂O₂ (P<0.05), and the half maximal inhibitory concentration of H₂O₂ was 0.7 mmol/L. Transfection with PDGFRα over-expression vector successfully induced high expression of PDGFRα at mRNA and protein levels in the PIGI cells, and increased the viability of the cells with H₂O₂ treatment (P<0.05). Over-expression of PDGFRα decreased the apoptotic rate of PIGI cells treated with H₂O₂ (P<0.05), and the level of ROS in the cells (P<0.05). The protein levels of cleaved caspase-3 and p-p38 were also decreased (P<0.05). CONCLUSION: PDGFRα inhibits the apoptosis of melanocytes induced by H₂O₂, partially reverses the growth inhibition of melanocytes by H₂O₂, and decreases the ROS level. The mechanism may be related to regulating the protein levels of p-p38 and cleaved caspase-3 in the cells.     

Influence of Sini decoction on the proliferation and apoptosis of artery smooth muscle cells after balloon injury

AIM: To investigate the influence of Sini decoction (SND) on the proliferation and apoptosis of rabbit abdominal aorta smooth muscle cells after ballon injury and discuss the effect of vascular smooth muscle cell's (VSMCs) proliferation and apoptosis in post-percutaneous coronary intervention (PCI) restenosis (RS) and the feasibility of SND preventing post-PCI RS. METHODS: The animal model of rabbit abdominal aorta ballon injury was set up and the therapertic group was treated with SND. The shape of proliferative and apoptotic cell were investigated by electron microscope. Immunohistochemistry staining was performed using α-actin,PCNA and Cyclin E monoclonal antibodies. In situ Cell Death Detection Kit was used to identify apoptotic cells. Abdomial aorta angiography was operated in the 84th day subgroup and the stenosis degree was evalued by quantitative angiographic analysis. RESULTS: As compared with the control group, the therapeutic group displayed a lower proliferative percentage and a higher apoptosic percentage (P<0.05). Moreover, the apoptosic peek time was on the 14th day after operation,which was longer than the control group. CONCLUSION: SND effectly inhibited the proliferation of VSMCs and iuduced apoptosis in VSMCs.     

Effects of bFGF on brain edema,nerve function injury and autophagy related protein in rats with traumatic brain injury

AIM:To study the effects of basic fibroblast growth factor (bFGF) on brain edema, nerve function damage and autophagy related proteins in rats with head injury. METHODS:The rat model of craniocerebral injury (CI) was constructed. The rats were divided into control group, CI group, and low-, middle-and high-dose bFGF groups (n=10). The CI model was established in CI group, while the rats in control group were not given epidural impact. The rats in low-dose, middle-dose and high-dose bFGF groups were given bFGF at 2, 4 and 6 μg, respectively, by intraperitoneal injection after 30 min. The neurological function in the rats was evaluated by improved neurological function scoring. The rat brain tissues were taken, and the water content was detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the brain tissue were measured by ELISA. The malondialdehyde (MDA) content was analyzed by thiobarbituric acid method. The activity of superoxide dismutase (SOD) was examined by WST-8 assay. The glutathine peroxidase (GSH-Px) activity was detected by colorimetric method. The protein levels of autophagy related proteins LC3-Ⅱ and beclin-1 in the brain tissues were determined by Western blot. RESULTS:The neurological function score was increased significantly of the rats in CI group. The rat model of craniocerebral injury was successfully constructed. Neurological function scores in the rats in low-dose, middle-dose and high-dose bFGF groups were reduced, the water content of the brain tissue was also reduced (P<0.05). The levels of TNF-α, IL-6 and IL-1 β were decreased in the brain tissues (P<0.05), the content of MDA was declined (P<0.05), the activities of SOD and GSH-Px were increased (P<0.05), the protein levels of LC3-Ⅱ and beclin-1 were decreased, compared with the untreated rats in CI group (P<0.05). CONCLUSION:bFGF improves the nerve function of the rats with craniocerebral injury, reduces the water content of the brain tissue, reduces the expression of autophagic protein LC3-Ⅱ and beclin-1.The mechanism is related to the inhibition of inflammatory reaction and oxidative damage.     

Effects of testosterone on endothelial function and intimal proliferation after balloon injury in male rabbit abdominal aorta

AIM: To investigate the effects of testosterone on endothelial function and intimal proliferation after balloon injury in male rabbit abdominal aorta. METHODS: 24 male New Zealand white rabbits were divided randomly into three groups: control group (n=8, sham castration), hypotestosteronemia group (n=8,castration) and testosterone replacement group (n=8,castration +testosterone undecanoate intramuscular injection,14mg/kg). Abdominal aorta was injured with 3 mm PTCA balloon after testosterone undecanoate had been injected for three days. Two weeks later, blood samples were obtained for detection of plasma testosterone, lipids, metabolic product of nitric oxide (NO₂^-／NO₃^-), superoxide dismutase(SOD) and malondialdehyde (MDA),and all the abdominal aorta were excised to be analyzed by computer. RESULTS: The intimal area of hypotestosteronemia group were significantly larger than that of other two groups(P＜0.01). plasma NO₂^-／NO₃^- and SOD levels were significantly decreased, while the total cholesterol(TC),triglycerides(TG), low density lipoprotein(LDL) and plasma MDA were significantly increased. No difference was observed between control group and testosterone replacement group in all parameters. CONCLUSION: Testosterone, at physiological level,had the effects of inhibiting the intimal proliferation and of protecting the endothelial function after balloon injury in male rabbit abdominal aorta.     

Effects of platelet-derived growth factor on DNA and collagen protein synthesis in human vascular fibroblasts

AIM: To investigate the effects of platelet-derived growth factor on DNA and collagen protein synthesis in human vascular fibroblasts. METHODS: In the present experiment, the human vascular fibroblasts were cultured and effects of platelet-derived growth factor-BB on DNA and collagen protein synthesis in human vascular fibroblasts were observed by using [³H]-TdR incorporation and [³H]-proline incorporation in vitro. RESULTS: Platelet-derived growth factor-BB significantly promoted NDA synthesis and collagen protein synthesis of quiescent human vascular fibroblasts, with a maximal response at a concentration of 30μg·L^-1at 24 h and 36 h, respectively. CONCLUSION: Platelet-derived growth factor-BB promotes DNA and collagen protein synthesis in cultured human vascular fibroblasts.     

Effect of heme oxygenase-1/endogenous carbon monoxide system on restenosis of rabbit carotid artery after balloon injury

AIM: To investigate the effect of heme oxygenase-1 (HO-1)/carbon monoxide (CO) system on restenosis of carotid artery after balloon angioplasty.METHODS: Fifty rabbits were randomly divided into 5 groups: control group given normal chow (C group), sham group(Sh group), 1.5% cholesterol diet group (Ch group), 1.5% cholesterol diet plus hemin group(Hm group)and zinc protoporphyrin IX group(Zn group).The experiment lasted for 10 weeks. At the beginning of the 3rd week, the animals in Ch group, Hm group and Zn group underwent balloon injury at one side of common carotid artery.RESULTS: Compared with those in C group, the production of arterial nitric oxide (NO) and activity of constructive nitric oxide synthase (cNOS) were significantly decreased, while CO production and HO-1 expression were significantly increased (all P<0.01) in Ch group. Compared with those in Ch group, the arterial CO production and HO-1 expression in Hm group were markedly increased, while the expression of endothelin-1 (ET-1), the intimal area and the ratio of intimal area/medial area(I/M) were distinctly reduced. Compared with those in Ch group, the arterial CO production and HO-1 expression in Zn group were obviously decreased, while the expression of ET-1, the intima area and the ratio of I/M were significantly increased.CONCLUSION: The HO-1/CO system improves the endothelium function and restrains neointimal proliferation by compensating and regulating NOS/NO system and lowering ET-1 expression so as to inhibit the restenosis.     

Retrovirus-mediated cellular repressor of E1A-stimulated genes inhibits neointima formation in the rat carotid artery after balloon injury

AIM: To evaluate the effects of over-expression of cellular repressor of E1A-stimulated genes (CREG) mediated by retrovirus on neointima formation in injured rat carotid. METHODS: The pluronic F127 containing pLNCX/CREG or pLNCX/GFP retroviral vectors was placed around the injured rat carotid.The neointima,media areas and the intima to media ratio were calculated.Expressions of CREG,SM α-actin and Ki-67 were detected. RESULTS: The GFP expression was observed at day 2 in pLNCX/GFP groups.The expression of exogenous CREG was also significantly increased in arteries at day 2 after pLNCX-CREG infection.Over-expression of CREG significantly suppressed neointima formation,attenuated the expression of Ki-67 and up-regulated SM α-actin expression. CONCLUSION: Over-expression of CREG inhibits VSMCs proliferation and promotes VSMCs differentiation after vascular injury.It suggests that modulation of CREG expression or activity may be a viable approach to treat neointimal restenosis after percutaneous coronary intervention.     

Effect of fucoidan on intestinal ischemia-reperfusion injury in rats

AIM:To investigate the effect and potential mechanism of fucoidan on intestinal ischemia-reperfusion (I/R) injury in rats. METHODS:Adult male Wistar rats were randomly divided into 3 groups:sham group, I/R group and Fucoidan+I/R group. Fucoidan at 160 mg/kg was intraperitoneally injected in rats of Fucoidan+I/R group 7 d prior to operation, and the equal volume of saline was intraperitoneally injected in rats of sham group and I/R group. The rats in I/R group and Fucoidan+I/R group underwent superior mesenteric artery occlusion for 1 h and then reperfusion for 2 h. Following reperfusion, the histomorphological changes of the ileum were examined by HE staining. The levels of diamine oxidase (DAO), D-lactic acid (D-LA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β were detected in the blood samples, the levels of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO), and the protein levels of Bax, cleaved caspase-3 and Bcl-2 were analyzed in intestinal tissue samples. RESULTS:Compared with sham group and Fucoidan+I/R group, the serum levels of DAO, D-LA, TNF-α, IL-6 and IL-1β were significantly increased in I/R group (P<0.05), Chiu's score of intestinal tissue, MDA content, MPO activity, the levels of Bax and cleaved caspase-3 protein in the intestinal tissues were also significantly increased (P<0.05), while the tissue GSH content, SOD activity, and Bcl-2 protein levels were significantly decreased (P<0.05). CONCLUSION:Fucoidan attenuates intestinal tissue damage caused by I/R, which may be related to anti-oxidation, anti-inflammatory and anti-apoptotic effects.     

Co-transfection of PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene prevents vascular anastomotic restenosis after coronary bypass

AIM: To elucidate the co-transfection of platelet derived growth factor B(PDGF-B) antisense oligonucleotide and tissue-type plasminogen activator gene to prevent vascular anastomotic restenosis after coronary bypass.METHODS: A dog model of vascular anastomotic restenosis after coronary bypass was constructed.A constructed tissue-type plasminogen activator(tPA) gene plasmid and a designed PDGF-B oligonucleotide were used to transfect into the dog cardiomyocytes and anastomotic vascular smooth muscle cells(VSMCs) at the same time of coronary bypass,using a therapeutic ultrasound for the gene delivery.Effects of these two genes on thrombosis in local anastomotic vessels,the expressions of proliferating cell nuclear antigen(PCNA) and PDGF-B mRNA by VSMCs and the proliferation of vascular intima were observed with the methods of routine pathological,immuno-histochemical staining,in situ hybridization and morphometry.RESULTS: PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene were succesfully transfected.These two genes significantly inhibited the expressions of PCNA and PDGF-B mRNA in intimal VSMCs with the inhibitory rates of 65.01% and 81.75%,respectively.The local intimal thickness and area also reduce markablely and the thrombosis of the anastomosis was prevented followed by the reduction of the anastomotic restenotic rate of 62.63%.CONCLUSION: Co-transfection of PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene inhibits the dog experimental anastomotic restenosis after coronary bypass.     

Effect of imatinib on myocardial fibrosis in DOCA-salt hypertensive rats

AIM: To investigate the effects of imatinib (IMA), one of platelet-derived growth factor receptor (PDGFR) inhibitors, on myocardial fibrosis in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Sixty male uninephrectomized SD rats were treated with 1% NaCl and 0.2% KCl in the drinking water for 4 weeks and assigned to 3 groups: vehicle control group (control group), DOCA treatment group (DOCA group), DOCA and IMA treatment group (DOCA+IMA group). Systolic blood pressure (SBP) was measured using the tail-cuff method. Myocardial tissue inflammation was analyzed by hematoxylin-eosin staining. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyzed by Sirius red staining. Ectodermal dysplasia-1 (ED-1) was analyzed by immunohistochemistry. Expression levels of platelet-derived growth factors (PDGF-A and PDGF-C), PDGF receptor α (PDGFRα) and phosphorylated PDGFRα (p-PDGFRα) were detected by Western blotting. RESULTS: SBP in DOCA group and DOCA+IMA group were signficantly higher than that in control group. No significant difference of SBP between DOCA group and DOCA+IM group was observed. In DOCA group, severe myocardial fibrosis was found, and CVF and PVCA were higher than those in control group. The differences of the CVF and PVCA between DOCA+IMA group and control group were detected, but the CVF and PVCA in DOCA+IMA group were significantly lower than those in DOCA group. Compared with control group, different degrees of myocardial tissue inflammation and monocyte/macrophage infiltration were observed in DOCA group and DOCA+IMA group. The expression levels of PDGF-A, PDGF-C and PDGFRα in DOCA group and DOCA+IMA group were much higher than those in control group, but the expression of p-PDGFRα in DOCA+IMA group were signficantly lower than that in DOCA group. CONCLUSION: Mineralocorticoid-induced myocardial fibrosis is related to cardiac tissue inflammatory response, excessive monocyte/macrophage infiltration and expressions of PDGF-A,PDGF-C and PDGFRα. Imatinib has an inhibitory effect on the myocardial fibrosis. The mechanisms may be associated with the inhibition of PDGFRα activity on the surface of fibroblast, thus interrupting PDGFs signaling-induced fibroblast division and proliferation.     

Effects of angiotensin converting enzyme inhibitor on the arterial elastase after balloon injury

AIM: To study the effects of angiotensin converting enzyme inhibitor (ACEI) on elastase after balloon injury. METHODS: The carotid arteries and aortas twelve-weeks-old Wistar male rats were injured by balloon catheter. The rats were divided into experimental and control groups in which ACEI (temocapril-HCl, 10 mg·kg^-1 ·d^-1) and the vehicle were administered 2 days before injury respectively and the animals were sacrificed on day 2, 3, 5 and 10, respectively. In situ hybridization, immunohistochemistry and elastase activity bioassay were used for studying elastase. RESULTS: The intimal area on day 10 in the experimental group was significantly suppressed compared to that in the control rats (P<0.01), positive cells for elastase mRNA, elastase and elastase activities in the media in the experimental groups, at 2, 3 and 5 days were significantly less than those in the control groups respectively (P<0.01, P<0.05). CONCLUSION: AECI (temocapril-HCl) obviously suppressed the elastase expressions and activities of the medial smooth muscle cells after arterial injury, it suggests that elastase expression is related to the involvement of ACE.     

Effects of Sini decoction on the expression of TGF-β1 in balloon injured iliac artery of rabbits

AIM:To investigate the effect of Sini decoction (SND) on vascular stenosis and the expression of transfoming growth factor-β1 (TGF-β₁) in iliac artery balloon injured rabbits. METHODS:24 male New Zealand albino rabbits were divided into three groups:control group, model group and SND treatment group. The iliac arteries were injured by balloon in model and SND groups. Four weeks later, serum TGF-β₁ level was assayed by ELISA. Endothelial hyperplasia, TGF-β₁ protein and mRNA expression were observed in injured iliac artery. RESULTS:Light microscope showed that the vascular lumina were narrower, intima was thicker in model group control and SND treatment group. The serum TGF-β₁ level was lower in control than model group and SND treatment group, and the serum TGF-β₁ level in SND treatment group was lower than that in model group. Immunohistochemistry and RT-PCR results showed that TGF-β₁ protein and mRNA expression was lower in rabbit iliac artery of control group than that in model group and SND treatment group, and the expression of TGF-β₁ protein and mRNA decreased significantly in SND treatment group compared with model group. CONCLUSION:SND could lessen intimal hyperplasia and vascular stenosis in balloon injured iliac artery, which might be related to decrease in TGF-β₁ protein and gene expression in iliac artery.      

Effects of bFGF on neuronal apoptosis and fractalkine expression in cerebral ischemia/reperfusion rats

AIM: To study the effects of basic fibroblast growth factor (bFGF) on neuronal apoptosis and fractalkine expression in ischemic penumbra after cerebral ischemia/reperfusion in rats.METHODS: Thirty-six rats were randomly divided into 3 groups: sham operation group, ischemia/reperfusion group and bFGF group. The model of middle cerebral artery occlusion was established by the method of intraluminal filament blockage. The middle cerebral arteries were blocked for 1 h and then reperfused for 24 h. Neurological performances of all rats were scored with Bederson's standard. The brain tissues of the rats were stained and the average infarct volume was calculated. TUNEL method was used to determine the number of apoptotic neurons, and the expression of fractalkine was detected by the method of immunohistochemistry.RESULTS: The score of neurological performances in bFGF group was 2.23±0.59, lower than that in ischemia/reperfusion group (3.18±0.65). The number of apoptotic neurons in bFGF group (13.22±1.35) was lower than that in ischemia/reperfusion group (17.28±1.01, P<0.05), which was the lowest in sham operation group (0.91±0.65). Compared with sham operation group, the expression of fractalkine in ischemia/reperfusion group was decreased. The expression of fractalkine in bFGF group was mainly higher than that in ischemia/reperfusion group (P<0.05).CONCLUSION: Up-regulation of fractalkine may be one of the molecular mechanisms of bFGF to protect neurons against ischemia/reperfusion injury.     

Effects of UTI on oxidative stress damage in rabbit brain tissues after cardiopulmonary resuscitation

AIM: To investigate the effects of ulinastatin (UTI) on oxidative stress damage in rabbit brain tissues after cardiopulmonary resuscitation (CPR). METHODS: The model of cardiac arrest (CA) in adult male New Zealand rabbits was established and the levels of malondialdehyde (MDA) and glutathione (GSH) in plasma 24 h after restoration of spontaneous circulation (ROSC) were detected. In another experiment, 48 CA New Zealand rabbits were used. After ROSC, the animals were randomly divided into model group and UTI treatment group. The effects of UTI on MDA, GSH and the apoptosis of neurons in the cortex and hippocampus were observed. The effect of UTI on the expression of nuclear factor E2-related factor 2 (Nrf2) was also analyzed. RESULTS: The concentration of MDA in plasma increased rapidly after CA and peaked at 2 h after ROSC, whereas the content of GSH dropped to a lower level. UTI restrained the rise of MDA in the cortex and hippocampus and increased the level of GSH. UTI also accelerated the activation of Nrf2. In the cortex and hippocampus CA1~CA3 areas, the number of apoptotic neurons in model group was more than that in UTI group. CONCLUSION: UTI evidently increases the expression of Nrf2 in rabbit brain tissues, elevates the level of GSH and decreases the concentration of MDA to protect cortical and hippocampal neurons.