Aim To establish and evaluate a mouse model of my-ocardial fibrosis by hypodermic injection of isoprenaline. Meth-ods Kunming mice were randomly divided into 2 groups, namely, the myocardial fibrosis model group and the control group, 10 mice in each group. The mice in the model group were given isoprenaline 5 mg · kg-1 by hypodermic injection. From the following day, the dose of isoprenaline was reduced to 2. 5 mg·kg-1 , and lasted for 30 days. The mice in the control group were treated with the physiological saline in the same way. Final-ly, heart weight was then weighed and the cardiac weight index (CWI) was calculated. Hydroxyproline (Hydro) level in myo-cardium was determined by a colorimetric method. HE and Mas-son’s trichrome staining were used to estimate the extent of myo-cardial fibrosis and calculate the collagen volume fraction ( CVF) . RT-PCR was used to measure the myocardial Collagen I mRNA expression. Results Compared with the control group, the CWI and Hydro content in the myocardial tissues in the model group were increased(P<0.01). The content of col-lagen in the myocardial tissues and the CVF were increased obvi-ously(P<0.01). The RT-PCR results showed that the left ven-tricle Collagen I mRNA expression in the model group increased obviously( P<0.01 ) . Conclusion Isoprenaline-induced myo-cardial fibrosis model has been established and the method is very simple, economic and reliable.

Aim To compare the pharmacological ac-tivity of icariin( ICA) and genistien ( GEN) against os-teoporosis after oral administration with them to growing rats and ovariectomized rats. Methods 25 mg·kg-1 icariin and 10 mg · kg-1 genistein ( equal in molar concentration) were administered to one-month-old fe-male SD rats every day for three months. Treatments at the same dosage were administered to the 6-month-old ovariectomized SD rats every day for three months. Their effects were compared on bone mineral density and biomechanical properties of femurs and vertebrae, serum levels of osteocalcin and tartaric acid phospha-tase 5b ( TRACP 5b) and histomorphometry. Results The results showed that, in young rats, icariin treat-ment significantly increased bone mineral density, the maximum mechanical loads of femurs and vertebrae as well as the bone qualities ( serum markers and microar-chitecture ) , whereas genistein treatment had little effects compared with the non-treatment control. How-ever, genistein treatment was more efficacious than icariin in preventing bone loss and deterioration of bone microarchitecture in ovariectomized rats. Conclusion Our data suggest that, since icariin has a higher os-teogenic activity but lower estrogenic activity, it has been found to be more efficacious than genistein in peak bone mass accrual only in young rats. In the ovariectimized rats, however, as the main force to pre-vent bone loss is the estrogenic activity, genistein has been found to be more efficacious than icariin in reduc-ing bone loss.

Aim To investigate the possible mecha-nisms of the levels of NO decrease induced apoptosis in human placental trophoblast cells. Methods Human placental trophoblast cells ( HTR-8 ) were cultured in 5 ml DMEM-F12 culture medium with 37℃ 5% CO2 . Then, the old culture medium was discarded and re-placed with 10,100,500,1 000 μmol·L-1 L-NAME, and the group without L-NAME was set as the control group, cultured for 48h. The effects of L-NAME on the survival of cells were detected by methylthiazolyldiphe-nyl tetrazolium bromide ( MTT); the content of NO in cells was tested by nitrate reductive enzymatic;trans-mission electron microscopy, flow cytometry analysis and Annexin-V FITC dyeing were used to test the effects of L-NAME on apoptosis in HTR-8 cells;restore Fe3+ colorimetric assay was applied for detection of to-tal antioxidant capacity ( T-AOC ) , xanthine oxidase for detection of superoxide dismutase ( SOD) activity, and thiobarbituric acid colorimetry for determination of content of MDA. Results Compared with the control group, the survival rate of HTR-8 cells and the levels of NO in 100,500,1 000 μmol·L-1 L-NAME group were significantly reduced(P<0.05,P<0.01). Flow analysis and Annexin-V FITC staining showed that L-NAME could induce cell apoptosis in a dose-dependent manner. The number of cell apoptosis was negatively correlated with the content of NO ( r = -0.5210 ) in HTR-8 cells. Transmission electron microscopy results showed that compared with the control group, the ex-perimental group's cell nucleus shape was irregular, nuclear pyknosis in irregular shape, the chromatin ag-glutination or side the collection, mitochondrial swell-ing or enrichment, crest fracture or dissolved, even vanished, forming the vacuole, especially in 100 μmol ·L-1 L-NAME group, the apoptotic bodies obviously appeared. At the same time, T-AOC, SOD levels in HTR-8 cells decreased ( P <0.05 ) , and the MDA content increased ( P<0.05 ) . The number of cell ap-optosis was negatively correlated with the level of T-AOC ( r= -0.3212 ) , SOD ( r= -0.2779 ) in HTR-8 cells , while positively correlated with the content of MDA(r=0.2807). Conclusion Oxidative stress may play an important role in the levels of NO decrease in-duced apoptosis in human placental trophoblast cells.

Aim To investigate the protective effects of hydrogen sulfide ( H2 S) on focal cerebral ischemia/reperfusion injury in rats and the possible mechanisms. Methods Male Sprague Dawley rats were divided into three groups randomly: sham-operated group, cerebral ischemia/ reperfusion ( I/R) group and sodium hydro-sulfide ( NaHS ) + I/R group. The left temporary middle cerebral artery occlusion ( MCAO ) model was established by the line-embolism method. After rats were suffered 2h/24h ischemia/reperfusion stress, the mortality rate was evaluated, and the nervous function-al defect degree was evaluated by Longe scoring, the volumes of cerebral infarction was evaluated by 2 ,3 ,5-triphenyltetrazolium chloride ( TTC) staining, and the expression of P2X7 receptor protein in brain tissue was detected by the immunofluorescence method. Results The mortality rate in NaHS + I/R rats ( 29.41%) was obviously lower than those of I/R group ( 42 . 86%) . The nervous defect scores in NaHS + I/R rats were significant lower than those of I/R group ( P <0.05 ) . The volumes of cerebral infarction in NaHS +I/R group (21.88% ±3.53%) were significant lower than those of I/R group ( 36.71% ±3.73%) ( P <0.01 ) . The results of immunofluorescence showed that the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of I/R group were significantly higher than those of sham-op-erated group(P<0. 01). However, compared with I/R group, the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of NaHS + I/R group were significantly decreased ( P<0. 01). Conclusions H2S exerts the neuroprotective effect on focal cerebral ischemia/reperfusion injury in rats, and the protective mechanism might be associated with down-regulating the expression of P2X7 receptor protein in brain tissue.

Aim To provide an electrophysiological basis for hippocampus involved emotional changes caused by tinnitus, the effects of salicylate on electro-physiological characteristics of the voltage-gated calci-um channels in hippocampal neurons were performed. Method The effects of salicylate on voltage-gated cal-cium channels in rat hippocampal neurons were stud-ied, using the whole-cell voltage clamp method. Re-sults Salicylate blocked the voltage-gated calcium channels ( ICa ) in a concentration-dependent manner (0.1~10 mmol · L-1 ) . The half-inhibition concen-tration ( IC50 ) values for the blocking action of salicy-late on ICa were 1.64 mmol·L-1 . With 1 mmol·L-1 salicylate applicalted into bath solution, the steady-state activation curve of calcium channel was shifted by about 9 mV in the hyperpolarizing direction, and its steady-state inactivation curve was not changed. Con-clusion Salicylate inhibits ICa in rat hippocampal neu-rons and significantly affects the activation kinetics of ICa ,which could be related to emotional changes caused by tinnitus.

Aim To explore the role of progesterone re-ceptor B ( PRB ) in regulation of medroxyprogesterone acetate ( MPA) sensitivity in endometrial cancer cells, and to investigate the effect of MPA on the biological character in Ishikawa cells infected with shRNA targe-ting PRB gene. Methods Ishikawa cells were stably transfected with PRB shRNA using lentivirus to knock-down endogenous PRB expression. Real-time fluores-cent quantitative PCR was applied to confirm the knockdown effect. MTT assay, flow cytometry and cell invasion assay were applied to detect the influence of MPA on endometrial cancer cell proliferation, apopto-sis and invasion. We also used Western blot assay to detect the effect of MPA induced the activation of ERK/MAPK signal pathway. Results Recombinant lentiviral vector expressing shRNA targeting PRB gene was successfully established, results of real-time PCR and Western blot showed that compared with control group, PRB expression in Ishikawa cells infected with shRNA decreased obviously ( P <0.01 ); MPA could repress endometrial cancer cells proliferation and inva-sion, meanwhile promoted its apoptosis ( P <0.01 ) . However, the effect was almost reverse in Ishikawa cells infected with shRNA. Furthermore, MPA induced ERK/MAPK activation in Ishikawa cells infected with shRNA. Conclusions PRB plays a role in regulating therapeutic sensitivity of MPA in endometrial cancer cells;and for Ishikawa cells infected with shRNA tar-geting PRB gene, MPA has effects on the biological character via pERK1/2-MAPK signal pathway.

Aim To investigate the effect of DHA on NGF-induced neuronal differentiation of PC12 cells and explore the possible mechanism via regulating BMP pathway. Methods PC12 cells were treated with 100μg·L-1 NGF and 100 μg·L-1 NGF + 10 μmol· L-1 DHA for 3, 6 and 9 days respectively. The length and number of neurite were detected by immunofluores-cenc. DHA content was analyzed by gas chromatogra-phy in all groups. The protein expression of BMP4, BMP7 , BMPR-II and p-Smad 1/5/8 was determined by Western blot. Results The length of total primary neurite in NGF+DHA groups was obviously increased, longer than that in NGF group; DHA content in 10μmol · L-1 DHA group was higher than that in the control group;NGF+DHA groups also unregulated the protein expression of BMP4 , BMP7 , BMPR-II and p-Smad 1/5/8 . Conclusion DHA promotes NGF-in-duced neuronal differentiation in PC12 cells, which may be associated with the upregulation of BMP path-way protein.

Depression is a worldwide neuropsychiatric disorder. Currently most preclinical and clinical studies of depression focus on monoaminergic system. However, there is growing evidence which suggests that glutamatergic system plays a critical role in the pathophysiology of depression. This review focuses on the de-velopment of new antidepressants that target glutamatergic sys-tem, summarizes the current mechanisms of antidepressants, and also highlights new insights to the pathophysiology of depression.

Aim To investigate the effects of echina-coside ( ECH ) on the learning and memory capacities and brain level of oxygen free radicals of rats with de-mentia induced by amyloid β-peptide. Methods Six-ty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats pergroup into 6 groups:sham operated group, model, ECH high dose (40 mg ·kg-1·d-1), ECH middle dose (20 mg· kg-1· d-1), ECH low dose (10 mg·kg-1·d-1) and Hup A (Huperzine A, 0. 02 mg·kg-1·d-1) group. Mor-ris maze tests were conducted for evaluating the learn-ing and memory ability. Content of malondialdehyde (MDA), nitric oxide (NO) and activities of superox-ide dismutase ( SOD) and NO synthase ( NOS) in the hippocampus and cortex were detected. ResultsAβ25-35 induced significant learning and memory im-pairment in the rats. Compared with the rats in model group, those treated with ECH at different doses all manifested alleviation of learning and memory impair-ment ( P<0 . 01 , P<0 . 05 ) . Cotents of MDA of ECH treatment group were obviously decreased, while SOD activities were obviously increased, and significantly reduced the release of NO and NOS in the hippocam-pus and cortex brain tissue ( P <0 . 01 , P <0.05 ) . Conclusion ECH can enhance the learning and mem-ory ability in rats with AD, which is presumably relat-ed to accelerating the cleaning of oxygen free radicals and reducing oxidative stress in brain of AD rats.

Aim To study the pharmacokinetic char-acteristics of serial compounds that took the scutellarin and scutellarein as lead compounds by using the model of in vitro liver microsomes, and to screen compounds whose medicinal properties were superior to scutellarin and scutellarein. Methods The content of candidate compounds at different times by incubation system of rat liver microsome was determined using UPLC-MS/MS method. Candidate compounds that contained opti-mum T1/2 and CLint were screened. Enzyme kinetics and conversions of candidate compounds were com-pared with those of scutellarin and scutellarein. Re-sults The T1/2 and CLint were optimum of W11 com-pared with those of scutellarin and scutellarein; the Vmax, Km and CLint of compound W11 were (10.25 ±2.59 ) μmol · min-1 · g-1 , ( 4.64 ±0.24 ) μmol · L-1 and ( 2.29 ±0.23 ) L · min-1 · g-1; the Vmax , Km and CLint of scutellarin were (45.95±9.50) μmol · min-1 · g-1 , ( 10.19 ± 1.66 ) μmol · L-1 and (4.48±0.20) L·min-1 ·g-1; W11 might be me-tabolized into scutellarin and M1 ( a compound with mo-lecular weight of 577 after demethylating ) . Conclu-sion The pharmacokinetic properties of candidate compound W11 are better than those of scutellarin, and it could release scutellarin.