Objective:To evaluate the therapeutic effects of sinomenine on T-helper cell type 1-mediated experimental colitis in-duced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Methods:Balb/c mice were divided into five groups:ethanol control group, TNBS model group, and sinomenine treatment groups (50, 100 and 200 mg·kg-1 ) with 10 ones in each. Colitis was induced by colonic instillation of TNBS dissolved in 0. 1 ml of 50% ethanol. Seven days after the colonic instillation of TNBS, sinomenine was given by gastric gavage once daily for 21 days. The mice were sacrificed on the 28th day, the injury degree of colonic mucosa was ob-served, the colon myeloperoxidase ( MPO) activity was determined, and the levels of inflammatory cytokines ( TNF-α, IL-17 and IL-23) were determined by ELISA. Results:Compared with those in TNBS model group, the body mass, gross injury score and histologi-cal findings in sinomenine groups at medium dose and high dose were significantly improved (P<0. 05), the activity of MPO signifi-cantly decreased (P<0. 05), and the protein levels of TNF-α, IL-17 and IL-23 in colonic mucosa were lower than those in TNBS group (P<0. 05). Conclusion:Sinomenine has notable therapeutic effect on TNBS-induced chronic colitis in mice, and the mecha-nism is related to the inhibition of Th1 cytokines by sinomenine.

Objective To explore effect of increasing cerebrospinal fluid (CSF) leptin level by administration from the foramen magnum to the cerebellum medulla oblongata pool in osteoporosis in rabbit model established by ovariectomy (OVX) and methylprednisolones.Methods According to certain inclusion and exclusion criteria,30 adult rabbits which were healthy 5-month-old female New Zealand white rabbits with the same batch and weight were divided into 5 groups (n=6) with random number table,including control group,normal saline group,Low dose group,middle dose group and high dose group.The animal model of osteoporosis (OP) was established 8 weeks after ovariectomy (bilateral ovarian resection) and intramuscular injection of methylprednisolone daily for 8 consecutive weeks in all groups.The control group were only simulated puncture and didn't inject any drugs or normal saline,the normal saline group were intracerebroventricular (ICV) injection with NS and Low,Middle and High dose group injected with low,middle and high dose of leptin respectively at 0,3,7 days after OVX.Before (0 week) and 4,8 weeks after the operation,the measure of dual energy X-ray absorptiometry was done on all the rabbits femur and bone mineral density (BMD) was delivered.Before (0 week) and 4,8 weeks after the first administration,leptin in cerebrospinal fluid (CSF) and serum growth hormone (GH),insulin growth factor 1 (IGF-1) and osteocalcin (OT/BGP) were tested with Enzyme linked immunosorbent assay and serum calcium,phosphorus and alkaline phosphatase (ALP) with automatic biochemical analyzer (ACA).The rabbits were sacrificed and the thalamus and femoral neck were harvested to test the expression of leptin receptor (LEPR) in thalamus and bone morphogenetic protein-2 (BMP-2) and type Ⅰ collagen (Col Ⅰ) at 8 weeks after the first administration.Results Compared with the control group and NS group,the cerebrospinal fluid (CSF) leptin concentration of leptin administration groups kept in a higher level significantly at 4 and 8 weeks after leptin administration,it was positively correlated with the concentration of administration.After administration 4 and 8 weeks,the bone mineral density (BMD) of leptin administration groups were not significantly lower than that of non-administration groups,and the high dose group was unchanged.The serum osteocalcin/bone glad protein (OT/BGP) concentration of leptin administration groups decreased more significantly compared with the non-administration groups at 4 weeks after leptin administration;and it rebounded more significantly than the non-administration groups and low dose group rebounded more significantly than other non-administration groups at 8 weeks.The concentration of serum growth hormone (GH) of 5 groups showed a downward trend at 4 and 8 weeks,the serum GH concentration of leptin administration groups decreased more significantly than the non-administration groups.The concentration of serum insulin-like growth IGF-1 of 5 groups were decreased significantly at 4 weeks,and the serum IGF-1 concentration of control and low dose groups were significantly higher than other 3 groups at 8weeks.Compared with the non-administration groups,the concentration of serum Calcium of leptin administration groups were increased more obvious,and it was positively correlated with the concentration of administration.Serum phosphorus of 5 groups were decreased at 4 weeks and elevated at 8 weeks;there was no difference among the groups.Serum ALP showed a continuous downward trend,and the middle dose group decreased significantly compared with other groups at 4 and 8 weeks.RTPCR results showed that the BMP-2 and Col Ⅰ mRNA expression increased and positively correlated with leptin administration concentration at 8weeks.Conclusion The increase of cerebrospinal fluid leptin level can promote the bone metabolism,reduce bone loss and precaution the occurrence of osteoporosis in rabbit model caused by OVX and methylprednisolone,and it was positively correlated with the concentration of administration.That provides a new method for the prevention and treatment of osteoporosis in rabbit model.

Objective To investigate the enhanced osteogenesis during bone fracture healing after intracerebroven-tricular (ICV) leptin injection, using rabbit model with created segmental bone defect in right tibial. Method Segmental critical-sized defects were created at the right tibial bone of skeletally mature New Zealand white rabbits. In experiment group (leptin group), recombinant rabbit leptin was injected into cerebellomedullary cistern through foramen magnum. While in control group, normal saline was injected in the same way. Bone Mineral Density (BMD) was evaluated by qCT at 1st, 3rd, 7th, 14th and the 21st days. At the 21st days, all rabbits were euthanized to collect the right tibia for histomorphology, to ex-amine the BMP-2 expression in the bone callus by Fluorescence in situ hybridization (FISH). Result In the leptin group, body weight declined more obviously than control group then it start to arise at the 14th day;qCT showed significant higher BMD in leptin group than in control group at the 7th day;FISH showed a higher BMP-2 expression in leptin group than in control group. Conclusion Cerebellomedullary leptin injection through foramen magnum could accelerate limb fracture healing in rabbit model with right tibial bone defection.

Objective To investigate effect of mild hypothermia on changes of somatosensory evoked potential (SEP) and synaptophysin mRNA level after traumatic brain injury (TBI) and determine hypothermia-induced neuroprotection.Methods Forty-five SD rats were allocated into mild hypothermia group,TBI group and sham operation group with 15 rats per group according to the random number table.Left-side fluid percussion impact was performed to induce models of TBI.Rats were exposed to hypothermia environment (32-35℃) for 6 hours in mild hypothermia group after TBI.Rats in sham operation group were treated by only drilling on left side of the head,rather than hitting.To evaluate function outcome,modified neurological severity score (mNSS),SEP and synaptophysin mRNA level were measured at 6 hours,24 hours and 7 days postinjury.Results The mNSS in mild hypothermia group lowered compared with TBI group,especially at 24 hours and 7 days (P ＜ 0.05).SEP in mild hypothermia group was significantly shortened at 6 and 24 hours compared with TBI group (P ＜ 0.05),but SEP revealed no significant difference among the 3 groups at 7 days (P ＞ 0.05).Level of synaptophysin mRNA in mild hypothermia group increased at 6 hours postinjury compared with TBI group [(0.08 ± 0.02) vs (0.12 ±0.04)],with further increase at 7 days postinjury[(0.06 ± 0.01) vs (0.33 ± 0.10)] (P ＜0.05).Conclusion The shortage of nerve conduction time of the injured side and promotion of nerve regeneration suggest the neuroprotective role of mild hypothermia following TBI.

Objective:To explore whether Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses.Methods:C57BL/6 mice were immunized with MOG35-55 peptides,and evaluated for clinical neurological score every day .10 mice of the EAE were injected with Tuftsin subcutaneously .The spinal cord were stained by the methods of Haematoxylin Eosinstain , Luxol Fast Blue stain.The mRNA expression of IL-10 and TNF-αfrom brian tissue were detected at the 28 days by RT-PC method.Results:The controlled mice had no symptoms of disease and HE ,LFB were normal.Comparison EAE group with Tuftsin group of HE,LFB,EAE group were server than Tuftsin group.The expression of IL-10 in Tuftsin group was higher than EAE group.The expression of TNF-αin Tuftsin group was lower than EAE group .Conclusion: Tuftsin can attenuates symptoms in experimental autoimmune encephalomyelitis mouses .

Objective To elucidate the constituents from the root of Euphorbia pekinensis and to look for new products with antitumor activity.Methods The chromatography on silica gel was used and the structures were identified by IR,NMR,and MS spectral analyses and their physicochemical properties were comparied.Results Eight compounds were isolated and identified as octadecanol(Ⅰ),octadecanyl-3-methoxy-4-hydroxybenzeneacrylate(Ⅱ),?-sitosterol(Ⅲ),triacontanoic acid(Ⅳ),2,2′-dimethoxy-3,3′-dihydroxy-5,5′-oxo-6,6′-biphenylformic anhydride(Ⅴ),euphol(Ⅵ),tirucallol(Ⅶ),and euphpekinensin(Ⅷ).Conclusion The compounds Ⅰ,Ⅳ,Ⅵ,and Ⅶ are isolated from the roots of E.pekinensis for the first time.

Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.

Objective To observe whether rabbit blood leptin can leak into the brain after craniocerebral trauma (CCT),and to dynamically detect serum levels of leptin,growth hormone (GH),and insulinlike growth factor-1 (IGF-1),and leptin level in cerebrospinal fluid (CSF) after CCT.Methods The FITC labeled leptin was injected into blood vessels of 15 adult male rabbits after anesthesia.Then 9 rabbits underwent unilateral fluid percussive impact,while 6 rabbits underwent sham operation.Thirty minutes postoperatively,brain tissue was taken to make frozen sections which were used to observe fluorescence labeled leptin range.Thirty three adult male rabbits were randomly divided into serum group,serum-control group,CSF group and CSF-control group.Rabbits in serum group and CSF group received fluid percussive impact,while rabbits in serum-control group and CSF-control group were drilled a 7 mm window in skull.Rabbits in serum group and serum-control group were phlebotomized 2 ml at 1 d,3 d,7 d and 14 d after operation,and rabbits in CSF group and CSF-control group were extracted CSF 0.5 ml at the same time points.Then serum levels of leptin,GH,and IGF-1,and leptin level in CSF were tested by ELISA.Results The fluorescence imaging could be seen in the injured brain tissue of rabbits with CCT,which was more than those in brain tissue of rabbits receiving sham operation.Serum leptin levels of rabbits in serum group at each time point were higher than those in serum-control group.Serum levels of GH and IGF-1 and leptin level in CSF were higher in rabbits with CCT than those in rabbits without CCT at 1 d,3 d and 7 d after operation.Conclusion The blood leptin can leak into the brain after CCT,which can cause increase of blood GH and IGF-1.And the latter may be the endocrine factors promoting fracture healing after CCT.

ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P ＜ 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P ＜0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.

Objective To study the expressions of erythmpoietin(EPO)and its receptors(EPOR)in the injured brain tissue ofthe rats with traumatic brain injury(TBI).Methods A total of78 SD rats were randomly divided into three groups including control group(six rats),sham group(36rats) and fluid percussion injury group(36 rats).The rats were sacrificed at 6,24 hours,3,5,7 and 14days after TBI in the sham group and the fluid percussion injury group(six rats at each time point).Then,the injured brain tissues were removed for observation of the mRNA and protein expressions of EPO and EPOR by meaDiB of real-time PCR and Western blot. Results The expression of EPO was increased at 24 hours and reached the peak at day 3 after TBI.The hish expression level of EPO could maintain for two days or so.began to decrease at day 7 and recovered to normal at day 14 after Till.While the expression of EPOR reached the peak at 24 hours after TBI and maintained hish level at day14. Conclusions The expressions of EPO and EPOR show increase within 24 hours after TBI.In fact,the expressions of both factors are not in consistency,with more transient expression of EPO.