亲代谢型谷氨酸受体配基对帕金森病大鼠的神经保护作用

目的探讨PD模型大鼠黑质致密部亲代谢型谷氨酸受体(mGluRs)的蛋白表达及其配基的药物治疗作用。方法6-羟基多巴单侧黑质损毁法建立大鼠PD模型。免疫组织化学法观察黑质致密部mGluR1a,2/3,4,5,8和酪氨酸羟化酶(TH)的表达,并用Nissl和Fluoro-JadeB荧光双染法在激光共集焦显微镜下观察退行性变的神经元。结果6-羟基多巴导致损毁侧mGluRs和TH免疫活性下降。Ⅰ组mGluRs拮抗剂和Ⅱ,Ⅲ组mGluRs激动剂能使治疗组相应的受体表达升高,尤其是mGluR5,mGluR2/3和mGluR4的蛋白表达。其中,以APDC组(Ⅱ组mGluRs激动剂)的保护效应最为显著。5个非假手术组退行性变细胞与正常细胞的比值(D/V)均有不同程度地增高。结论mGluRs可能参与PD的发生、发展过程。Ⅰ组mGluRs拮抗剂和Ⅱ组mGluRs激动剂具有一定的神经保护功能。     

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.     

伽玛刀低剂量照射对致疒间大鼠海马中氨基酸递质的影响

目的观察伽玛刀低剂量照射对致疒间大鼠海马中谷氨酸(Glu)、γ-氨基丁酸(GABA)的影响,探讨伽玛刀治疗癫疒间的作用机制。方法将50只锂-匹罗卡品致疒间大鼠随机分为照射组和非照射组,各25只,另取正常大鼠25只(腹腔注射生理盐水)作为对照组。照射组大鼠进行伽玛刀低剂量照射(周边剂量20Gy),对照组和非照射组大鼠不进行伽玛刀照射。用高效液相色谱-质谱-质谱(HPLC-MS-MS)分析法检测各组大鼠海马Glu、GABA的含量。结果伽玛刀照射2周后,照射组和非照射组大鼠海马中Glu含量均高于对照组,照射组GLu含量低于非照射组,差异具有统计学意义(P0.05);照射组和非照射组GABA含量均低于对照组,照射组GABA含量高于非照射组,差异具有统计学意义(P0.05)。结论伽玛刀低剂量照射通过调节海马中Glu与GABA的平衡,以达到抗癫疒间的作用。     

脑内注射抗脑抗体后的脑损害研究

目的研究抗脑抗体对脑组织的损害作用。方法 24只兔随机分为3组,抗脑抗体组、抗脑抗体＋免疫抑制治疗组、生理盐水对照组,分别皮层注射抗脑抗体或生理盐水,治疗组隔日口服环孢素软胶囊50 mg/只（共4周）。1个月后处死兔,取注射点周围皮层组织,用免疫组化法测定谷氨酸表达,用TUNEL法测定细胞凋亡情况。结果兔脑组织注射抗脑抗体1个月后谷氨酸表达以及凋亡均明显高于对照组和治疗组。结论升高的抗脑抗体导致神经细胞凋亡和谷氨酸表达增高,自身免疫参与继发性脑损害,免疫抑制治疗能够减轻抗脑抗体引起的继发性脑损伤。     

前庭传入冲动对大鼠前庭神经内侧核区内谷氨酸含量的影响

[目的]探讨麻醉大鼠前庭传入冲动对前庭神经内侧核（MVN）区内谷氨酸含量的影响．[方法]采用脑部微量透析法和高效液相色谱法,观察麻醉状态下20g／L利多卡因中耳内灌注短时阻断及40℃温水中耳刺激大鼠外周前庭器官后同侧MVN区内谷氨酸含量的变化．[结果]中耳内灌注40℃温水刺激大鼠外周前庭器官后同侧MVN区内谷氨酸含量与基础值相比较无明显差异;利用20g／L利多卡因短时阻断左侧前庭传入后同侧MVN区内谷氨酸含量较基础值明显降低．[结论]阻断麻醉大鼠前庭传入可降低MVN区内谷氨酸含量．     

灯盏花素对大鼠脑微血管内皮细胞损伤的保护作用

目的观察灯盏花素对谷氨酸致原代培养的大鼠脑微血管内皮细胞(rBMECs)损伤的保护作用。方法灯盏花素(200、100、50μmol/L)作用于rBMECs 24 h后,加入谷氨酸(终浓度为1 mmol/L)培养18 h,MTT法检测rBMECs细胞活性,并按试剂盒方法检测细胞上清液中乳酸脱氢酶(LDH)水平、细胞中丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性。结果谷氨酸(l mmol/L)使原代培养的rBMECs明显受到损伤,灯盏花素高、中浓度(200、100μmol/L)可显著对抗谷氨酸造成的rBMECs损伤,抑制LDH释放,降低MDA水平,增强SOD活性。结论灯盏花素对谷氨酸所致原代培养的rBMECs损伤具有明显的保护作用,其机制与增强细胞抗氧化能力有关。     

Safety and healing efficacy of Sea buckthorn (Hippophae rhamnoides L.) seed oil on burn wounds in rats

The present investigation was undertaken to determine the safety and efficacy of supercritical CO₂-extracted Hippophae rhamnoides L. (Sea buckthorn) (SBT) seed oil on burn wound model. SBT seed oil was co-administered by two routes at a dose of 2.5 ml/kg body weight (p.o.) and 200 μl (topical) for 7 days on experimental burn wounds in rats. The SBT seed oil augmented the wound healing process as indicated by significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control and reference control treated with silver sulfadiazine (SS) ointment. Histopathological findings further confirmed the healing potential of SBT seed oil. SBT seed oil treatment up-regulated the expression of matrix metalloproteinases (MMP-2 and 9), collagen type-III and VEGF in granulation tissue. It was observed that SBT seed oil also possesses antioxidant properties as evidenced by significant increase in reduced glutathione (GSH) level and reduced production of reactive oxygen species (ROS) in wound granulation tissue. In acute and sub-acute oral toxicity studies, no adverse effects were observed in any of the groups administered with SBT seed oil. These results suggest that the supercritical CO₂-extracted Sea buckthorn seed oil possesses significant wound healing activity and have no associated toxicity or side effects.     

High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature

Although systematic review and meta-analysis of randomized controlled trials (RCTs) have concluded that vitamin K is effective in preventing fractures, the effect of vitamin K on the skeleton remains a matter of controversy. The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for RCTs by using the search terms “vitamin K₁ or vitamin K₂,” “bone,” and “postmenopausal women” and the following inclusion criteria: approximately 50 or more subjects per group and study period of 2 years or longer. Seven RCTs met the inclusion criteria. The results of these RCTs showed that vitamin K₁ and vitamin K₂ supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K₁ and vitamin K₂ supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K₁ and vitamin K₂ supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.