基于大鼠脑缺血再灌注损伤模型建立芍药内酯苷的PK-PD模型

[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。     

Effect of forsythiaside A on immune function in rats with ulcerative colitis

AIM To investigate the effect of forsythiaside A (FA) on immune function in rats with ulcerative colitis and its related mechanism. METHODS Healthy SD rats were randomly divided into 5 groups: control group (no treatment, normal feeding), model group (establishment of rat ulcerative colitis model), and low, medium and high doses of FA groups (treatment of the model rats with FA at 5 mg/kg, 20 mg/kg and 80 mg/kg, respectively). The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in rat colon tissues were measured by colorimetry, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2) and IL-4 were detected by ELISA. The spleen index and thymus index, the percentages of CD3⁺, CD4⁺ and CD8⁺ T-lymphocytes in peripheral blood mononuclear cells （PBMC）, the serum IgA and IgG levels, and the serum complement C3 and C4 levels were also determined. RESULTS The colon tissues of the rats in model group showed obvious inflammation and ulceration, indicating that the animal model was successfully established. Compared with model group, the colonic inflammation and ulceration were significantly attenuated in FA groups, among which the high dose had the best effect. Compared with control group, the spleen index and thymus index of the rars in model group were decreased (P<0.05), MDA content in colon tissues was increased (P<0.05), and SOD activity in colon tissues was decreased (P<0.05). The levels of CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ T-lymphocytes in PBMC, and the serum levels of C3, C4 and IL-4 were decreased (P<0.05), while the serum levels of IgA, IgG, TNF-α, and IL-2 were increased in model group as compared with control group. Furthermore, the spleen index and thymus index of the rats in FA groups were increased (P<0.05), the MDA content in the colon tissues was decreased (P<0.05), and the SOD activity in the colon tissues was increased (P<0.05). The levels of CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ T-lymphocytes in PBMC, and the serum levels of C3, C4 and IL-4 were increased (P<0.05), while serum IgA, IgG, TNF-α and IL-2 levels were decreased in FA groups as compared with model group (P<0.05). CONCLUSION Forsythiaside A effectively attenuates the colonic lesions in rats with ulcerative colitis, and its mechanism may be related to reinforcement of oxygen free radical scavenging power, alleviation of inflammatory response, and enhancement of immune function.     

Ontogeny of glutathione and glutathione-related antioxidant enzymes in rat liver

We conducted a comprehensive characterization of the ontogeny of glutathione (GSH) and its related enzymes in rat liver. GSH content and activities of glutathione reductase (GR), cytosolic glutathione-S-transferases (GST), and glutathione peroxidase (GPx) were determined in male rat livers (n = 4) at different developmental stages. Our results indicate total hepatic GSH content and GR, GST, and GPx activity were low in the perinatal period. GSH content remained relatively constant throughout postnatal development, but GR, GST, and GPx activity underwent significant increases to attain adult levels by late post-weaning. Whether the ontogenic pattern of GSH and its related enzymes explain, in part, the altered susceptibility of neonates to some toxicants requires further investigation. Our study provides fundamental biological information on the ontogeny of cytosolic antioxidant/detoxification enzymes in a relevant toxicological risk assessment species. Additional studies are needed to fully characterize the ontogeny of other xenobiotic detoxification enzymes to further promote the rat as a developmental toxicology model that can identify toxicokinetic reasons for differences in susceptibility to toxicity between the neonate and adult.     

Altered pharmacokinetics of enrofloxacin in experimental models of hepatic and renal impairment

We investigated the effects of hepatic and renal impairment on the pharmacokinetics of enrofloxacin in Sprague-Dawley rats. Experimental hepatic and renal failure were induced by carbon tetrachloride (CCL₄) and 5/6 nephrectomy, respectively. After intravenous dosing of enrofloxacin (10 mg/kg), plasma concentrations of enrofloxacin were measured using liquid chromatograph/mass spectrometry. There was no significant effect of hepatic impairment on enrofloxacin pharmacokinetics. However, renal impairment markedly prolonged elimination half life (t_1/2λz) of enrofloxacin (P < 0.05), comparing with respective control. Total body clearance (Cl_b) and volume of distribution at steady state (V_ss) were significantly decreased (P < 0.05) by renal impairment. In conclusion, these results suggested that renal impairment could affect the pharmacokinetics of enrofloxacin.     

壮阳促孕散对肾阳虚大鼠垂体和睾丸组织形态的影响

[目的]研究中药壮阳促孕散对肾阳虚大鼠垂体和睾丸组织形态的影响。[方法]用氢化可的松造大鼠肾阳虚模型,造模7 d,造模同时中药治疗组和阳性对照组灌胃给药13 d。处死大鼠后迅速摘取垂体和睾丸,制作垂体、睾丸切片,观察组织形态变化。[结果]造模后,模型对照组出现明显的阳虚症表现,垂体和睾丸组织发生退行性改变,阳性对照组、中药治疗组垂体和睾丸组织退行性改变得到改善。[结论]中药壮阳促孕散可使肾阳虚大鼠垂体、睾丸组织形态的退行性改变得到改善,对垂体-性腺轴的调节功能有促进作用。     

Evidences of osteoporosis improvement in Wistar rats treated with Ginkgo biloba extract: A histomorphometric study of mandible and femur

This study was aimed at investigating the anti-osteoporotic effects of the extract of Ginkgo biloba (EGb) in glucocorticoid-induced-osteoporosis. A significant reduction was observed in the percentage of the bone of the osteoporosis group in both the mandible and femur. The EGb group treated with 28 and 56 mg/Kg showed a significant increase in the percentage of trabecular bone (PTB) of the femur. The percentage of the alveolar bone of the mandible (PAB) had a significant increase with all doses of EGb. The treatment with EGb significantly reversed the loss of the PAB of the mandible and of the PTB of the femur.     

和龙膨润土的不同饲喂量对小鼠的繁殖和体重的影响

本试验是在饲料中添加不同比例的膨润土，对小鼠进行了生长饲喂试验和Ｆ０代两胎繁殖试验，结果表明，添加１％和３％的膨润土与其它组相比，小鼠增重、仔鼠出生重、出生存活率和哺育存活率等差异极显著（Ｐ＜０．０１）或差异显著（Ｐ＜０．０５），且３％尤为明显．母鼠怀孕率、妊娠率在添加１％、３％膨润土时也明显高于其它两组．     

一种建立大鼠心肌肥厚的简便方法

[目的]介绍一种简便的建立大鼠心肌肥厚模型的方法。[方法]健康成年SD大鼠20只,试验组（10只）皮下注射异丙肾上腺素（ISO）,对照组（10只）皮下注射生理盐水。计算2组大鼠HW/BW、LVW/BW;观察2组大鼠心脏的组织病理变化;检测血清乳酸脱氢酶、总抗氧化能力、碱性磷酸酶的活力及丙二醛的含量。[结果]与对照组相比,试验组大鼠的HW/BW、LVW/BW均明显升高;心肌细胞直径明显变大,细胞间质增多,细胞间距变大;血清中乳酸脱氢酶、碱性磷酸酶的活力及丙二醛的含量明显升高,而血清总抗氧化能力明显降低。[结论]大鼠心肌肥厚模型造模成功,该方法技术简便,容易掌握。     

Effects of CSF-1,IL-1α on CSF-1 receptor gene expression in rat dental follicle cells

AIM: To study the effects of colony stimulating factor(CSF-1) and IL-1α on CSF-1 receptor mRNA levels and to determine if the autocrine effect is inhibited through the CSF-1 receptor.METHODS: Rat dental follicle cells were cultured in vitro.The effects of different concentrations of CSF-1 and IL-1α on CSF-1 receptor gene expression were detected by means of RT-PCR.RESULTS: High concentrations of CSF-1 reduced the gene expression of the CSF-1 receptor. IL-1α had no effects on CSF-1 receptor mRNA levels.CONCLUSION: High concentrations of CSF-1 inhibit the expression of CSF-1 receptor.IL-1α has no effect on the expression of CSF-1 receptor mRNA.