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??OBJECTIVE To observe the effect of Dracocephalum heterophyllum flavonoids(DHBF) of Uygur Medicine on cardiomyocyte hypertrophy, which were induced by angiotensin ??(Ang??), and it could provide a basis for further study to the mechanism. METHODS SD rats,0-3 d of age, neonatal rat myocardial cells cultured in vitro, the experiment was divided into control group, Ang??(1 ??mol??L^-1)group, different concentrations of DHBF(10, 25, 50 ??mol??L^-1)+Ang??(1 ??mol??L^-1) groups, cardiomyocyte hypertrophy were induced by Ang?? 1 ??mol??L^-1 and was intervened using DHBF respectively, CCK-8 method was used to observe the activity of myocardial cells,RT-PCR technique was used to detect the expression of m RNA of cardiac hypertrophy gene atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP),the internal factor was glyceraldehyde-3-phosphate dehydrogenase(GAPDH) .Confocal laser scanning was used to detect the surface area of myocardial cell was [Ca²⁺]_i;the activity of Ca²⁺-ATP was measured by the enzymatic reaction of fragmentation cell; the concentration of NO and the activity of NOS were determined by colorimetry. RESULTS Compared with the control group, the activity of myocardial cell was(85%??5%) in the Ang??group,which was increased significantly after it was dealed with DHBF and Ang??(P<0.05);RT-PCR results showed the expression of mRNA of ANP and BNP were increased by using Ang??, which were lower by using DHBF and Ang??. The surface area of myocardial cell were increased by using Ang??, which could be reversed by using DHBF and Ang??. Confocal laser scanning showed the concentration of[Ca²⁺]_i was increased by using Ang??,but which was lower significantly by using DHBF and Ang??(P<0.05). The enzymatic reaction of fragmentation cell results showed the activity of Ca²⁺-ATP was decreased by using Ang??, but which was increased significantly by using DHBF and Ang??(P<0.05). Colorimetry results showed the concentration of NO and the activity of NOS were decreased by using Ang??, but which was increased significantly by using DHBF and Ang??(P<0.05). CONCLUSION DHBF can improve the activity of hypertrophy cardiomyocytes which were induced by ang??, downregulate expression of mRNA of ANP and BNP, reduce surface area of cardiomyocytes induced by Ang??,the mechanism of action may be related to promoting the release of NO, regulating the concentration of[Ca²⁺]_i and the activity of Ca²⁺-ATP.     

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??OBJECTIVE To discuss the effect and mechanism of cinepazide maleate (CM) on myocardial injured rats induced by isoproterenol (Iso). METHODS Fifty male and female rats were divided into normal group, model group, the low and the high dose group of the CM, and captopril (Cap)positive control group. The rat model of myocardial injury was established by subcutaneous injection of Iso (5 mg??kg^-1??d^-1)for 7 d, rats in treatment group were given intraperitoneal injection of CM on the second day (1.5,3 mg??kg^-1??d^-1), rats in positive control group were given intragastric administration of Cap(10 mg??kg^-1??d^-1), and rats in normal group and model group were given intraperitoneal injection of normal saline in the same volume, for 14 d. The rats in each group were tested before and after treatment by three times of running endurance test. After stopping drug all rats were anesthetized for measuring the electrocardiogram (ECG), then taken blood for measuring the activities of serum SOD, LDH and CK, and taken hearts for measuring heart weight index (HWI), left ventricular mass index (LHWI), the contents of myocardial hydroxyproline (Hyp)and MDA, and observing the morphological changes of myocardial tissue by HE staining. RESULTS Compared with rats in normal group, rats in model group showed endurance value decrease, ECG abnormalities (arrhythmia and myocardial ischemia in waveform), increased HWI, LHWI (P<0.01), myocardial Hyp content, myocardial MDA level, and the level of serum LDH and CK, and reduced the serum SOD activity (P<0.05 or P<0.01). Compared with model group, CM could significantly increase endurance value, improve abnormal phenomenon of ECG, lower the HWI, LHWI, myocardial Hyp content, myocardial MDA level, and serum LDH and CK levels were lower, and serum SOD activity increased, especially in high dose group of CM (P<0.01). HE staining showed in the model group rat ventricular remodeling, myocardial rupture, a large number of collagen fibers, in the treatment group, ventricular remodeling and myocardial fibrosis were significantly improved. CONCLUSION Cinepazide maleate has protective effect on myocardial injury of rats induced by Iso.     

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??OBJECTIVE To investigate the influence and mechanism of different doses of Yangxinshi on infarction region angiogenesis of Wistar rats after acute myocardial infarction. METHODS Sixty healthy male Wistar rats were randomly divided into five groups, named as follow:group A: rosuvastatin group (0.75 mg??kg^-1??d^-1), group B: high-dose Yangxinshi(0.27 g??kg^-1??d^-1),group C:mid-dose Yangxinshi group (0.18 g??kg^-1??d^-1),group D: Low-dose Yangxinshi group (0.09 g??kg^-1??d^-1),group E:saline control group. A, B, C, D group was respectively given the drug by gavage, group E received normal saline by gavage. The models of acute myocardial infarction can be established in the forth week . After continued drugs for 4 weeks, rats were killed before detected blood biochemicalindexes such as blood lipids, liver and kidney function. Myocardial tissue was sliced and stained infarcted myocardium by HE to observe the pathological changes, also extract ischemic and infarct myocardium tissue protein and test VEGF protein expression with immunohistochemistry. RESULTS Myocardial tissue HE staining were observed a lot of survival island cardiomyocytes and neonatal thin-walled capillaries in four treatment groups , however,control group exist less normal cardiomyocytes and capillaries mainly disappear. Immunohistochemistry RESULTS showed high-doses of Yangxinshi group express higher VEGF protein compared with mid-dose group, low-dose group and control group, the difference was statistically significant (P<0.05), VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference was statistically significant (P<0.05). CONCLUSION Yangxinshi promote production of VEGF protein and angiogenesis of ischemic myocardium ,in addition its role and its dose is positive correlated. VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference is statistically significant (P<0.05).     

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??OBJECTIVE To investgate the protective effects and mechanisms of Polygonatum kingianum on nonalcoholic fatty liver induced by high-fat diet in rats. METHODS A total of 42 rats were randomly divided into normal control group (normal saline), model group (normal saline), resveratrol group (positive control, 40 mg??kg^-1) and low-, middle-and high-dose P. kingianum group (1, 4, 8 g??kg^-1). They were intragastrically given corresponding compounds (or normal saline) once a day, lasting for 14 weeks. Nonalcoholic fatty liver was induced by feed with high-fat diet for 14 weeks in those groups except for normal control group. Blood was taken from the corneas at 0, 6, 12 and 14 week, and then the levels of triglyceride (TG) and total cholesterol (TC) in serum were determined. Afterword, the rats were sacrificed at 14 week followed by the measurement of organs indices of liver??spleen and kidney, as well as the detection of levels of TC, TG, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in liver tissues. Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), ATP synthase and respiratory chain complex ?? and ?? in hepatic mitochondria were determined. RESULTS Nonalcoholic fatty liver was successfully induced by high-fat diet in rats. The different doses of water extract of P. kingianum could significantly inhibit the increasing of liver index and serum TC in high-fat diet-induced rats, alleviate swelling, degeneration, necrosis and inflammatory injury of hepatic cells, inhibit the increasing of TC, TG and LDL-C and decrease of HDL-C in liver tissues, as well as inhibit the exaltation of MDA level and reduction of SOD, GSH-PX, ATP synthase and respiratory chain complex ?? and ?? activity in hepatic mitochondria. CONCLUSION P. kingianum shows protective effects on high-fat diet-induced nonalcoholic fatty liver in rats. The action mechanism may be related to the elimination of oxidative stress product (MDA) and improvement of antioxidant enzyme activity (SOD and GSH-PX) in hepatic mitochondria, as well as the improvement of energy metabolism obstacle.     

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??OBJECTIVE To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS Araloside A was administered in a dose of 50 mg??kg^-1 via gastric in fusion and 5 mg??kg^-1 by intravenous injection in rats.Araloside A was analyzed by a validated LC-MS/MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS The RESULTS of pharmacokinetic study showed that the linear range of araloside A was good in 1.0-10 000.0 ??g??L^-1(r>0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg??kg^-1 and intravenous injection of araloside A 5 mg??kg^-1 were as follows:t_1/2 was(8.65??3.22) and(2.00??0.21)h, AUC_0-t was(277.14??101.00) and (21 194.59??4 385.13)ng??h??L^-1, MRT_0-t was (7.88??0.64) and (1.21??0.11)h, Vd/F was (2 229.99??1 013.97) and (0.71??0.20)L??kg^-1, CL/F was(149.11??62.28) and (0.24??0.05) L??h^-1??kg^-1, respectively; ??_max was (32.68??10.74) ??g??L^-1 for intragastric administration and t_max reached(1.21??0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.     

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??OBJECTIVE To investigate the inhibitory effect and possible mechanisms of puerariae isoflavone(PI) on prostatic hyperplasia induced by testosterone propionate.METHODS Forty-eight male Wistar rats were randomly divided into six groups according to their body weight including normal control group, model group, 40, 80, 160 mg??kg^-1??d^-1 PI group, and finasteride positive control group. In addition to the sham operation for rats in the normal control group, the rats in other five groups performed castration surgery. After the restoration, the five groups of rats were subcutaneously injected with testosterone propionate (10 mg??kg^-1??d^-1) for 10 d to establish a benign prostatic hyperplasia model and then the subcutaneous injection was maintained every 2 d. High, middle and low dose PI groups were intragastrically administered (40, 80, 160 mg??kg^-1??d^-1) from the second day when the benign prostatic hyperplasia model was successfully constructed. The positive control group was given finasteride (1.0 mg??kg^-1??d^-1) .Rats in normal and model groups were given an equal volume of saline for 28 d. After the last administration, the prostate and seminal vesicles were separated under anesthesia in rats, the wet weight and volume of the prostate and seminal vesicles were measured. The prostate and seminal vesicles index were calculated too. Rat blood was drawn and dihydrotestosterone(DHT) and estradiol (E2) in the serum were measured. Nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels in prostate tissues were measured. The prostate tissue in each group was randomly selected for HE staining. The pathological structure of the prostate tissue was observed under an optical microscope.RESULTS Compared with the normal control group, the prostate gland index and seminal vesicle gland index of the model group increased significantly (P<0.01), and the DHT and E2 levels in serum increased significantly (P<0.01). MDA content was increased while NO levels, NOS and SOD activities were significantly decreased (P<0.01). HE staining showed that the size of the prostate gland in the model group was different, there were obvious dilation, hyperplasia and papillary protrusions, and the cavity was full of pink and homogeneous density. The interstitial tissue showed obvious dilations of blood vessels, infiltration of inflammatory cells, and proliferation of fibrous connective tissues. Compared with the model group, the index and volume of prostate and seminal vesicles in the PI and positive control groups were significantly decreased (P<0.05 or P<0.01), and the levels of serum DHT and E2 in the middle and high doses PI groups were significantly lower (P<0.05 or P<0.01). In all treatment groups, MDA content was decreased and NO, NOS, and SOD levels were increased (P<0.05 or P<0.01) except the low-dose PI groups. There was moderately hyperplasia in low-dose PI group, mild prostatic hyperplasia in positive control group and middle-dose PI group, basically no hyperplasia in high-dose PI group.CONCLUSION PI has a certain inhibitory effect on prostate hyperplasia induced by testosterone propionate, especially in the medium and high dose PI groups. The mechanism may be related to the effects of pueraria isoflavone on antioxidant,free radical scavenging in vivo, increasing NOS activity and increasing NO level.     

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??OBJECTIVE To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC_{0-12 h} were(43.62??16.20) and(42.02??14.40)mg??h??L^-1(P>0.05);??_max were (17.85??11.32) and (13.96??5.11) mg??L^-1(P>0.05);t_max were (2.72??1.74) and(1.32??0.42)h(P<0.05); ??₀ were (1.63??1.18) and (1.66??0.93) mg??L^-1(P>0.05); ??₁₂ were(1.84??2.09) and (1.81??1.76) mg??L^-1(P>0.05); CL were (14.12??5.30) and (19.66??5.99) L??h^-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.     

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??OBJECTIVE To investigate the anti-inflammatory effects of extract of Scutellaria baicalensis Georgi (SGE) and underlying mechanism by using LPS-induced microglial BV2 cells. METHODS MTT assay was used to observe the cell viability. The content of NO in cell supernatant was measured by Griess reagent. The levels of IL-1??, IL-6 and TNF-?? were detected by ELISA kits. The intracellular TLR4 expression was assayed by Western blotting. RESULTS The levels of NO, IL-1??, IL-6 and TNF-?? were significantly increased induced by LPS in the supernatant of BV2 cells (all P<0.01). However, co-treatment with SGE 100 ??g??mL^-1 significantly decreased the production of related inflammatory factors including NO (P<0.01), IL-1??(P<0.01), IL-6 (P<0.01) and TNF-?? (P<0.05). Furthermore, SGE significantly inhibited the TLR4 expression induced by LPS in BV2 cells. CONCLUSION SGE is able to alleviate LPS-induced inflammatory responses in BV2 cells through down-regulation of TLR4 protein expression suggesting that SGE has therapeutic potential for the treatment of neuroinflammatory diseases.