银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

目的 观察银杏叶提取物(GbE)对雄性SD糖尿病大鼠肾脏基质金属蛋白酶2(MMP-2)和Ⅳ型胶原表达的影响,从而探讨银杏叶对糖尿病肾病的保护机制.方法 24只链脲佐菌素诱导的SD大鼠完全随机分成糖尿病对照组(DM组)和GbE组,并以12只正常雄性SD大鼠作为正常对照组(NC组).分别于4、8周后,观察各组大鼠体重、肾重、随机血糖、尿蛋白排泄率等生化指标,并用免疫组化和逆转录聚合酶链反应方法 观察糖尿病大鼠肾脏MMP-2及Ⅳ型胶原的表达.结果 糖尿病大鼠的随机血糖、体重、肾脏/体重明显下降,尿白蛋白排泄率明显升高[DM组(31.59±4.59)mg/24 h比NC组(8.74±2.08)mg/24 h,P＜0.05],GbE组糖尿病大鼠尿白蛋白排泄率[(21.38±3.86)mg/24 h]较DM组有所下降(P＜0.05).8周时,与正常对照组相比,DM组大鼠肾小球MMP-2蛋白的表达水平明显下降[(0.49±0.07)mg/24 h比(0.15±0.04)mg/24 h,P＜0.05],而GbE组DM组大鼠肾小球MMP-2蛋白的表达水平[(0.48±0.07)mg/24 h]较DM组无明显下降(P＞0.05);DM组大鼠Ⅳ型胶原的表达水平较NC组明显升高[(3.48±0.54)mg/24h比(1.68±0.51)mg/24 h],而GbE组糖尿病大鼠较NC组无明显升高[(2.55±0.50)mg/24 h比(1.68±0.51)mg/24 h].结论 GbE可通过抑制糖尿病大鼠MMP-2过表达,进而对糖尿病肾病发挥保护作用.

Abstract：

Objective To study the effect of ginkgo biloba extract (GbE) on the expression of matrix metalloproteinase (MMP)-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups: diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group ( P ＜0.05 ). The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats ( P ＜ 0.05 ) but showed no changes in GbE treatment group compared to diabetes group( P ＞ 0.05 ). The expression level of type Ⅳ collagen was significantly increased in diabetic rats( P ＜0.05 ) but showed no changes in GbE group( P ＞0.05). Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.     

自发性2型糖尿病大鼠肺组织α平滑肌肌动蛋白表达的变化及罗格列酮对其影响

目的 探讨自发性2型糖尿病(OLETF)大鼠肺组织α-平滑肌肌动蛋白(α-SMA)表达的变化及罗格列酮对其影响.方法 30周龄雄性OLETF大鼠16只,分为OLETF组和OLETF/L组每组8只,对照组为8只LETO组大鼠.OLETF/L组大鼠给予罗格列酮3 mg/(kg·d)灌胃12周后处死大白鼠,应用免疫组织化学和免疫蛋白印迹法检测各组大鼠肺组织α-SMA蛋白表达.结果 各组大鼠肺组织α-SMA主要表达于肌成纤维细胞、血管平滑肌细胞、小气道平滑肌,OLETF组大鼠肺组织α-SMA蛋白表达(2.03±0.64)明显高于LETO组(1.18±0.35),P<0.05];OLETF/L组明显减少(1.34±0.40),差异均有统计学意义(均P<0.05).结论 OLETF大鼠肺组织肌成纤维细胞生成增多,罗格列酮可抑制成纤维细胞向肌成纤维细胞的转化,早期改善糖尿病肺纤维化.

Abstract：

Objective To investigate the changes of expression of α—smooth muscle actin(α-SMA)in lung of spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty(OLETF)rats and the effect by tlle rosiglitazone.Methods Totally 16 male OLETF rats in 30 weeks old were divided into OLETF group and OLETF／L group.The Long Evans Tokushima Otsuka(LETO)rats were in control group.Thle OLtErI’F.rats were given gastric lavage bymsiglitazone 3 ms／(kg·d)then were killed after 12 weeks.The levels of ct-SMA in lung of three groups were detected by immunohistochemistry and western blotting.Results α-SMA in lung of three groups mainly expressed in myofibmblast.vascular smooth muscle cells and small airway smootII muscle.Compared to control group,tlle levels of α-SMA in lung of OIJETF group were increased obviously(2.03-4-0.64 VS 1.18 4-0.35,P<0.05).Compared to OLETF group,the levels of α-SMA in lung of OLETF／L group were decreased obviously(1.34 ±0.40 VS 2.03 ±0.64.P<0.05).Conclusion Myofibroblast increases in lung of OLETF rats.Rosiglitazone can inhibit the transformation from fibroblast to myofibroblast and improve pulmonary fibrosis in diabetes in early stage.     

胶原关节炎大鼠滑膜组织核转录因子κB与白细胞介素1β和基质金属蛋白酶9相关性分析

目的 探讨白细胞介素1β(IL-1β)、基质金属蛋白酶9(MMP-9)、核因子κB(NF-κB)与类风湿关节炎发生发展的相关性.方法 构建Ⅱ型胶原诱导的胶原关节炎大鼠模型,分不同时点处死动物,检测滑膜细胞中IL-1β,NF-κB和MMP-9的表达,分析大鼠关节炎评分与滑膜细胞NF-κB、IL-1β、MMP-9的表达的相关性.结果 实验组造模前关节体积为(2.18±0.16)ml,造模后2、4、6周分别为(4.68±0.49)、(5.62±0.59)、(5.44±0.66)ml,与造模前比较,差异均有统计学意义(P＜0.01);对照组造模前和造模后2、4、6周关节体积分别为(2.15±0.26)、(2.38±0.32)、(2.19±0.31)、(2.18±0.26)ml.造模后2、4、6周实验组大鼠关节体积与对照组比较,差异有统计学意义(P＜0.01).实验组大鼠造模后2、4、6周关节指数分别为(8.00±0.32)、(9.80±0.66)、(9.40±0.51),与对照组(均为0)比较,差异有统计学意义(P＜0.05).大鼠关节指数与NF-κBp65呈显著正相关(r=0.593,P＜0.05);MMP-9与NF-κBp65呈显著负相关(r=-0.506,P＜0.05).结论 实验组大鼠滑膜组织中NF-κB与IL-1β表达水平显著高于正常对照滑膜组织,且与关节炎的评分有一定相关性;提示NF-κB在类风湿关节炎发病机制中起关键的调控作用.

Abstract：

Objective To investigate the corelation among interleukins-1β (IL-1β), matrix metalloproteinase 9 ( MMP-9), nuclear factor kappa B (NF-κB) and arthritis index (AI) in the development of arthritis, and to understand the pathology of synoviocyte. Methods Thirty-six female Wistar rats were randomly divided into two groups,namely the model controlled group and the normal controlled group; three subgroups were randomly divided into model group and controlled group. The model group rats were immunized with emuusified bovine type Ⅱ collagen in complete Freund'adjuvant by introdemal injection to induce collagen induced arthritis (CIA) on day1, day14 and day 28, while the controlled group were injected with saline at the same time. The model and the controlrats were killed at different times. We detected the expression and activation levels of IL-1β, MMP-9 and NF-κB in synovial tissue by immunohistochemistry. Then we analyzed the corelation between AI and the expression of IL-1 β, MMP-9 and NF-κB in the synovium and IL-6 and TNF-α in the serum. Results The joint volume of model group was (2. 18 ± 0. 16), (4.68 ± 0.49 ), (5.62 ± 0. 59), (5.44 ± 0.66 ) respectively before, 2, 4 and 6 weeks after setting up models. There were statistically significant differences between before and after setting up models ( P ＜ 0. 01 ).The joint volume of control group was ( 2. 15 ± 0.26), (2.38 ± 0.32), (2. 19 ± 0. 31 ), ( 2.18 ± 0.26 ) respectively before, 2, 4 and 6 weeks after making model. Through measuring joints sizes after successfully modeling 2, 4 and 6 weeks, there were statistically significant differences between model and control group( P ＜0.01 ). MMP-9 showed significant negative correlation with NF-κB P 65 ( r = -0. 506, P ＜ 0.05 ). Conclusions The expression levels of IL-1 β and NF-κB are significantly higher in CIA synovial than those in control group and show a positive correlation with AI. NF-κB plays acritical role in the pathology of RA via regulating inflammation reaction, facililating the prolifteration of synoviocyte and participating the reestablishment of articulation.     

Effect of N-acetylcysteine on Nrf2, heme oxygenase-1 and γ-glutamate cysteine synthetase in rats with chronic hepatic injury北大核心CSCD

OBJECTIVE To observe the effect of N-acetylcysteine on nuclear factor-eythroid 2 related factor 2(Nrf2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine synthetase(γ-GCS) in rats with chronic hepatic injury. METHODS The rats were divided into normal control and model groups. 25% CCI4olive oil solutiond mL·kg-1) was given by subcutaneous injection to induce a chronic hepatic injury rat model, 3 times a week, for 4 weeks. At the end of the 4th week, rats with chronic hepatic injury were equally divided into 5 groups: NAC 45, 90 and 180 mg·kg-1 groups, glutathione (GSH) 54 mg·kg-1 group (positive model group) and model group. Normal control and model groups were given the same volume of sterilized normal sodium, once a day, for 4 weeks. At the end of the 8th week, all the rats were sacrificed. The levels of glutamate pyruvate transaminase(GPT), glutamic oxaloacetic transaminase (GOT) in serum and superoxide dismutase(SOD), malondialdehyde (MDA), glutathione (GSH) and hydroxyproline(Hyp) in hepatic tissue were detected. Liver histopathological changes were observed. Immunohistochemistry was used to detect the expression of Nrf2, HO-1 and y-GCS in hepatic tissue. The mRNA levels of Nrf2, HO-1 and γ-GCS in the liver were detected by realtime PCR. RESULTS Compared with normal control group, levels of GPT, GOT, MDA and Hyp were raised(P<0.01), while protein expresssion of Nrf2 and HO-1 and γ-GCS, levels of SOD and GSH had no statistical difference. There was extensive adipose degeneration in hepatic cells in model group, and round vacuoles of different size were seen in hepatic tissue. Some hepatic cells developed edema, and portal areas were infiltrated with inflammatory cells. Compared with normal control group, GPT and GOT in serum, SOD, GSH and Hyp in hepatic tissue in NAC groups were decreased(P<0.05, P< 0.01). Compared with positive control group, Hyp in hepatic tissue declined obviously in NAC 45, 90 and 180 mg· kg-1 groups (P<0.01). Nrf2 expression in NAC 45 mg· kg-1 groups increased obviously (P<0.01). Compared with NAC 45 mg· kg-1 group, Nrf2 expression in NAC 90 and 180 mg· kg-1 groups declined (P<0.05, PO.01). CONCLUSION Low-dose broncholysin could protect against oxidative stress and prevent chronic hepatic injury by regulating the expression of Nrf2, HO-1 and γ-GCS.     

Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

OBJECTIVE To investigate the effect ofα-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. METHODS A mouse model of impaired learning and memory was created by ethanol(2.0 g · kg~(-1), ig). α-Asarone(7.5, 15 and 30 mg·kg~(-1), ip) was delivered 10 min prior to ethanol administration. After 40 min, the locomotor activity of mice with learning and memory impairment was evaluated by the open field test and the behavioral effect of α-asarone was evaluated using the novel object recognition test.Glutamate(Glu) and γ-aminobutyric acid(GABA) levels in the hippocampus were determined by ELISA, and the proteins expression levels of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor(Glu R2), N-methyl-D-aspartic acid(NMDA)receptor(NMDAR2 B), synaptophysin I(SYNΙ), glutamate transporter type 1(GLT-1) and calcium/calmodulindependent protein kinaseⅡ(Ca MKⅡ) were detected by Western blotting. RESULTS There was no significant difference in the horizontal or vertical locomotor activity between the ethanol and normal groups or the 7.5, 15 and 30 mg·kg~(-1)α-asarone groups[F(5, 48)=0.6536, P>0.05; F(5, 49)=1.995, P>0.05]. The recognition index in the ethanol group was significantly decreased as compared with that in the normal group[F(5, 46) =6.739, P<0.05]and was markedly increased in the α-asarone groups as compared with that in the ethanol group(P<0.05), with the exception of the 7.5 mg · kg~(-1)α-asarone group(P>0.05). The hippocampal Glu: GABA ratio in mice was significantly elevated in the ethanol group as compared with that in the normal group(33.42±0.8972 vs 30.79±0.2102, P<0.05) and significantly lower in the α-asarone groups(31.99±0.4986 vs. 33.42±0.8972; 30.97±0.1757 vs. 33.42±0.8972; 30.83 0.1723 vs. 33.42±0.8972, P<0.05). The expression levels of GluR2, NMDAR2B, pSYNⅠand p Ca MKII were significantly higher in the ethanol group as compared with those in the normal group(P<0.05) and obviously lower in the α-asarone groups(P<0.05), with the exception of GluR2, NMDAR2B and pCaMKⅡ in the 7.5 mg·kg~(-1)α-asarone group(P>0.05).And the expression level of GLT-1 was significantly lower in the ethanol group as compared with that in the normal group(P<0.05) and obviously higher in the α-asarone groups(P<0.05). CONCLUSION Pretreatment with α-asarone significantly improved the learning and memory impairment. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.     

Inhibitory effect of combination of tanshinone I,metformin and aspirin on malignant melanoma model mice北大核心CSCD

OBJECTIVE: To explore the antitumor effects of combined tanshinone I (Tan I), metformin (Met) and aspirin (Asp) on malignant melanoma in mice and the possible mechanisms. METHODS: C57BL/6 mice were injected with 0.1 mL B16F10 cells (2.8×109 L-1) to establish the subcutaneous transplantation tumor model at the right forelimbs axillary. Then, the mice were divided into 8 groups according to body mass, including model group, Tan I group (20 mg.kg-1 ip), Asp group (210 mg.kg-1, orally in drinking water), Met group (70 mg.kg-1, orally in drinking water), Asp+Met group, Tan I +Asp group, Tan I +Met group and Tan I +Asp+Met group, 10 mice in each group. Each mouse drank about 7 mL of water every day for a total of 18 d. The mouse body mass was measured every other day and the tumor diameter was calculated every day. The mice were sacrificed after treatment, the tumor mass was measured and the tumor inhibitory rates were counted. The histopathological changes of the liver and spleen were observed with HE staining. The percentage of lymphocytes in the tumor tissue such as CD8T, CD4+T and Treg cells was detected by flow cytometry. Inflammatory factors such as interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. RESULTS: The body mass (including tumor mass) of mice in different groups increased during the experiment, but that of Tan I + Asp+Met group increased more slower than in model group (P<0.01). At the end of the experiment, no lesions were seen in any liver or spleen tissue by pathological observation, and the number of survivors was 8/10 (model group), 8/10 (Tan I group), 7/10 (Asp group), 7/10 (Met group), 8/10 (Tan I +Asp group), 8/10 (Tan I +Met group), 7/10 (Asp + Met group) and 5/10 (Tan I +Asp+ Met group), respectively. Compared with model group, there were no obvious changes in tumor volume or tumor mass in Tan I, Asp and Met groups and other two-two joint groups, but the tumor volume and tumor mass in Tan I + Asp+ Met group were significantly decreased (P<.01, P<0.05), and the tumor inhibitory rate in this group was 46.2%. Compared with the model group, the percentage of CD8+T cells increased (P<0.05) in Tan I + Asp+ Met group, but there were no significant changes in other groups. The contents of IL-6, IL-1β and TNF-α in tumor tissue of Tan I +Met group were much higher than in model group (P<0.01, P<.05, P<0.05) and the content of IL-6 increased in Tan I +Asp+Met group (P<0.01). CONCLUSION: Combination of Tan I, Asp and Met can effectively inhibit the growth of melanoma in mice, which may be related to the increasing percentage of CD8+T lymphocytes and IL-6 in tumor tissue. However there are possibly some side effects. © 2017 Chinese Journal of Pharmacology and Toxicology. All rights reserved.     

长春西汀对慢性阻塞性肺疾病大鼠炎症干预作用的探讨

目的 探讨长春西汀对慢性阻塞性肺疾病(COPD)慢性炎症的作用.方法 将40只雄性Wistar大鼠随机分为正常对照组、COPD模型组、长春西汀5 mg/kg组、2.5 mg/ks组和1.25 mg/ks组,每组8只.采用熏香烟加气管内注入脂多糖法建立COPD大鼠模型.长春西汀组(共3组)从注入脂多糖次日起给予长春西汀腹腔注射,每日1次.观察各组大鼠肺组织病理改变,检测血清中肿瘤坏死因子(TNr)-a、白细胞介素(IL)-8、C反应蛋白(CRP)的浓度以及支气管肺泡灌洗液(BALF)中TNF-a、IL-8的浓度.结果 COPD模型组肺组织病理改变符合人类COPD的病理特点;长春西汀5 mg/kg组和2.5 mg/kg组病理改变较模型组轻;上述两组血清IL-8浓度分别为(18.40±2.40)和(19.30±3.11)ng/L,比COPD模型组[(23.81±3.54)ns/L]低,血清TNF-a浓度分别为(39.34±3.43)和(40.47±3.09)ns/L,比COPD模型组[(46.65±4.42)ns/L低],血清CRP浓度分别为(4.28±0.22)和(4.35±O.26)ms/L,比COPD模型组[(4.69±0.19)ms/L]低;上述2组肺泡灌洗液中IL-8浓度分别为(20.09 ±2.88)和(21.03±2.21)ng/L,低于COPD模型组[(25.02±2.92)ng/L],TNF-a浓度分别为(40.41±4.40)和(41.18±5.33)ng/L,低于COPD模型组[(48.81±4.92)ng/L],差异均有统计学意义.长春西汀1.25 mg/ks组各项指标与COPD模型组比较,差异无统计学意义(P>0.05).结论 长春西汀能降低COPD大鼠血清和BALF中炎性因子的水平,减轻气道及肺组织炎症,对COPD大鼠的炎症反应有一定的抑制作用.

Abstract：

Objective To observe the effect of vinpecetine on inflammatory factors and lung pathology of the rats with chronic obstructive pulmonary disease(COPD),and to investigate the therapeutic action of vinpecetine on COPD.Methods Totally 40 Wistar rats were randomly divided into the normal control group,the COPD model group and three viupocetine treated groups.The COPD rat model wag established by intratracheal instillation of lipepalysaceharide and exposure to cigarette smoke.The three intervention groups were intrapedtonealy injected with vinpecetine respectively at the dose of 1.25 mg/kg,2.5 mg/kg and 5 mg/kg before exposing to cigarette smoke.Pathologic changes of the lung tissue,interlukin(IL)-8 and tumor necrosis factor (TNF)-a levels in bronchial alveolarhvage fluid(BALF)and seruln,and CRP level in the serum were determined.Results The pathological changes in the COPD rat model were coincident with the changes in human.Compared with the COPD model group,the two groups treated with vinpecetine at the dose of 2.5 mg/kg and 5 mg/kg showed a significan t decrease in IL-8[(18.40 ±2.40)ng/L,(19.30±3.11)ng/L respectively vs(23.81±3.54)ng/L],TNF-a[(39.34±3.43)ng/L,(40.47±3.09)ns/L respectivelyvs (46.65±4.42)ng/L],and CRP[(4.28±0.22)mg/L,(4.35±0.26)mg/L respectively vs(4.69±0.19)mg/L]in serum.In the BALF of those the BALF of those two groups, the levers of Ⅱ-8[(20.09 4±2.88)ng/L,(21.03±2.21)ng/L]and TNF-a[(40.41±4.40)ng/L,(41.18 4±5.33)ng/L]were also significantly lower than those in the moder group[(25.02±2.92).g/L,(48.81±4.92)ng/L].The vinpocetine treated group at the dose of 1.25mg/kg ad no significant difference, compared with the COPD model group. Conclusions Vinpocetine can reduce the levels of inflammatory factors in BALF and the serum of the rats with COPD and decrease inflammation of the airway and lung tissue. Accordingly vinpecetine can inhibit the inflammation of the COPD rat model.     

机械性创伤致急性肺损伤大鼠血清肿瘤坏死因子α的动态变化和机制

目的 探讨血清肿瘤坏死因子α(TNF-α)在机械性创伤致急性肺损伤大鼠中的动态变化和机制.方法 将雄性Wistar大鼠40只完全随机分为伪创伤组和创伤组、伪急性肺损伤组和急性肺损伤组,每组10只,利用Noble-Collip创伤仪制备机械性创伤模型,腹腔注射TNF-α制作急性肺损伤模型.全部大鼠均于造模后6 h腹主动脉采血处死,采用ELISA法测定血清TNF-α含量,肺组织行常规组织病理学检查.结果 创伤组大鼠血清TNF-α含量明显高于伪创伤组[(335±28)mg/L比(177±10)ng/L],差异有统计学意义(P＜0.01).病理结果 显示:创伤组和急性肺损伤组肺组织炎症非常明显,而伪创伤组和伪急性肺损伤组基本正常.结论 机械性创伤大鼠血清中TNF-α含量的升高可能与机械性创伤后急性肺损伤有关.动态观察机械性创伤后血清中TNF-α的变化,有助于病情的评估及预后判断,具有重要的临床意义.

Abstract：

Objective To determine the dynamic changes and mechanism of tumor necrosis factor-α(TNF-α) in serum in acute lung injury(ALI) induced by mechanical trauma in mechanical trauma rat model. Methods Totally 40 male Wistar rats were randomly divided into sham group and trauma group, sham-acute lung injury group and acute lung injury group. Noble-Collip drum was used to establish mechanical trauma rat model. Intraperitoneal injection of TNF-α established acute lung injury model. All rats after modeling of abdominal aortic blood sampling time points were killed and the serum levels of TNF-α were asasyed by ELISA. Results Serum TNF-α levels (334. 78 ±± 28) ng/L in the trauma group were significantly higher than those in the sham group( 177 ±10 ) ng/L (P ＜0. 01 ). The pathological results showed that both in trauma group and acute lung injury group lung infection were very obvious, while it was basically normal in both sham group and sham-acute lung injury group. Conclusions Serum TNF-αt levels of mechanical trauma may be associated with acute lung injury after mechanical trauma. Therefore, dynamic observation of the change of serum TNF-α after mechanical trauma will help the assessment and prognosis of the disease, it has important clinical significance.     

The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism; [蛇 ? 多糖对大鼠乙酸型胃溃疡的治疗作用 ? 机制]北大核心CSCD

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

番茄红素对寰枢椎失稳老龄小鼠记忆的影响

Objective To observe the effect of Lycopene on the improvement of memory abilities by cumulating lactic acid for long time in atlas dentata vertebrae senile mice. Methods Totally 30% lactic acid 30μL one time every week was injected into the place between the first and the second cervical vertebrae for 3 weeks. Forty mice were randomized into five groups:young control group, model group, VitE group(50 mg/kg), control group,and two therapeutic groups of lycopene which was intragastric at the doses of 5, 2.5 mg/kg once everyday. The changes of memory in mice were observed with water-maze test and step-down avoidance test. The activities of acetylcholine esterase(AchE), and the content of acetylcholine, (Ach) in encephalon were tested. HE staining in mice brain, including the cortex and hippocampus was demonstrated. Results Compared with model group. Lycopene high dose could significantly shortened the latency period and wrong times in water-maze test (P ＜0.01 ), In stepdown avoidance test, the reaction period was shortened significantly ( P ＜ 0.01 ) and the latency period was shortened significantly. The activities of ChE decreased (P ＜0.01 ) and the content of ACh increased in the Lycopene high doses group(P＜0.01 ). The therapeutic groups of lycopene had less pathological change of cellular necrosis,neuron loss in hippocampal CAI than the model group. Conclusion Lycopene has a certain protective and improving effect on the decline of memory ability and cervical lesion induced by lactic acid in atlanto-axial joint cumulating.     

阿霉素诱发局灶节段性肾小球硬化肾病大鼠模型的建立

目的 建立临床表现和病理特点与人类肾小球疾病相似的阿霉素肾病大鼠模型.方法 将40只SD大鼠完全随机分为造模组(32只)和对照组(8只),造模组完全随机分为首次注射阿霉素后2周组、4周组、8周组、12周组,每组各8只.造模组大鼠尾静脉分2次注射阿霉素,第1次注射按6 mg/kg给药,第2次子1周(7 d)后按4 mg/kg给药;对照组按照造模组方法经大鼠尾静脉2次注射等量生理盐水.检测各组大鼠24h尿蛋白量、血清总蛋白、白蛋白、CH、TG、BUN、Cr的变;双抗体夹心酶联免疫吸附方法检测各组大鼠血清基质金属蛋白酶( MMP)2、MMP-9、转化生长因子(TGF) -β1;免疫组化方法检测各组大鼠纤维连接蛋白(FN)和层粘连蛋白(LN)的表达化;光镜、电镜观察2组大鼠肾脏病理变化.结果 造模组24h尿蛋白定量明显增加,8周末达高峰.造模组大鼠2周、4周、8周和12周组与对照组相比,血清总蛋白、白蛋白明显降低[(50.7±3.6)、(42.2±3.4)、(40.4±3.1)、(41.7±3.3)g/L比(62.8±2.8) g/L、(22.2±1.8)、(16.4±1.7)、(14.8±2.1)、(13.0±2.2)g/L比(29.0±1.3)g/L];TG、CH明显升高[(5.2±1.4)、(6.1±1.5)、(7.3±1.5)、(7.2±1.2)mmol/L比(0.6±0.3)mmol/L,(3.8±1.7)、(5.6±1.9)、(8.6±2.7)、(9.6±1.6) mmol/L比(1.3±0.1)mmol/L];MMP-2、MMP-9降低[(151.4±2.4)、(100.5±3.1)、(76.5±3.6)、(83.7±3.1)μg/L;(73.4±2.7)、(58.9±2.2)、(35.4±2.0)、(33.3±1.5) μg/L],血清TGF-β1含量升高;肾组织FN、LN的表达和分布范围均明显增加.造模12周在可见部分肾小球出现局灶节段性硬化.结论 采用阿霉素首次大剂量(6mg/kg)冲击诱导,1周后小剂量(4mg/kg)给药的方法,大鼠在12周末可见部分肾小球出现局灶节段性硬化.     

活血降糖胶囊对糖尿病肾病大鼠足细胞相关分子蛋白表达的影响

目的：探讨活血降糖胶囊对糖尿病肾病（DN）大鼠足细胞相关分子蛋白Nephrin、Podocin、CD2AP表达的影响。方法：应用单侧肾脏切除结合小剂量STZ单次腹腔注射方法建造DN大鼠模型,随机分为模型组（M组）、假手术正常对照组（N组）、活血降糖胶囊干预治疗组（H组）,每组6例。H组给予活血降糖胶囊的剂量折合生药2.5 g·kg^-1·d^-1灌胃,M组和N组给予等量纯化水灌胃。8周后检测各组大鼠的24 h尿蛋白定量、血生化等指标,应用免疫组化技术检测肾组织Nephrin、Podocin、CD2AP蛋白表达的情况。结果：8周后,与N组比较,M组出现24 h尿蛋白定量增多,内生肌酐清除率（Ccr）下降（P<0.05）,肾组织Nephrin、Podocin、CD2AP蛋白表达水平均下调（P<0.05）;与M组比较,H组24 h尿蛋白定量降低（P<0.05）,Ccr升高（P<0.05）,肾组织Nephrin、Podocin、CD2AP蛋白表达水平均上调（P<0.05）。采用直线相关分析后发现,24 h尿蛋白定量与肾组织Nephrin、Podocin、CD2AP蛋白表达水平呈负相关;Ccr与肾组织Nephrin、Podocin、CD2AP蛋白表达水平呈正相关。结论：DN时存在足细胞相关分子Nephrin、Podocin、CD2AP蛋白表达异常,活血降糖胶囊对DN大鼠肾脏的保护作用机制可能是通过增加足细胞相关分子nephrin、podocin、CD2AP蛋白表达,减少蛋白尿而实现的。     

霉酚酸酯对糖尿病大鼠肾组织Nephrin与Podocin表达的影响及机制

目的探讨霉酚酸酯(Mycophenolate mofetil,MMF)对糖尿病大鼠肾组织Nephrin与Podocin蛋白表达的影响及机制。方法建立链脲佐菌素诱导的单侧肾切除大鼠糖尿病模型,将模型大鼠随机分成糖尿病组(DM组)与MMF给药组(DM+MMF组,10mg·kg-1.d-1灌胃给药),另设对照组(C组)。8wk末检测血糖、24h尿白蛋白排泄率(AER)变化,通过免疫组化方法检测肾组织ED-1表达,Westernblot方法检测肾组织Nephrin、Podocin、白细胞介素-1(IL-1)与肿瘤坏死因子-α(TNF-α)蛋白表达。结果DM组大鼠尿AER明显高于C组(P<0.01),DM+MMF组大鼠尿AER明显低于DM组(P<0.05)。DM组大鼠肾小球ED-1阳性细胞数明显高于C组(P<0.01),DM+MMF组肾小球巨噬细胞浸润明显低于DM组(P<0.05)。DM组肾组织Nephrin与Podocin表达较C组分别下降80.2%与65.1%,MMF可明显恢复肾组织Nephrin与Podocin表达(P<0.01)。DM组肾组织IL-1与TNF-α表达较C组分别增加2.8倍与3.8倍,MMF可明显降低肾组织IL-1与TNF-α表达(P<0.01)。结论MMF可能通过恢复糖尿病大鼠肾组织Nephrin与Podocin蛋白表达减少尿白蛋白排泄。     

分清化浊胶囊对阿霉素肾病大鼠的影响

目的 观察分清化浊胶囊对阿霉素肾病大鼠的影响及其可能的作用机制。方法 将雄性SD大鼠随机分为6组（对照组,模型组,阳性对照组,分清化浊胶囊低、中、高剂量组）,除对照组外,其余各组大鼠采用尾iv阿霉素法制成阿霉素肾病大鼠模型,第一次尾iv阿霉素（4 mg/kg）1周后,第二次iv阿霉素（3.5 mg/kg）。造模成功后,对照组和模型组ig生理盐水,阳性对照组ig黄葵胶囊混悬液;其余治疗组ig分清化浊胶囊混悬液。每日一次,疗程4周。观察大鼠一般情况,在给药前、给药7、14、21、28 d测定24 h尿蛋白定量,末次给药后,测定大鼠血清总蛋白（TP）、白蛋白（ALB）、总胆固醇（TC）、三酰甘油（TG）、血尿素氮（BUN）、肌酐（Cr）,并观察大鼠肾脏病理变化。结果 治疗前,与对照组比较,各治疗组尿蛋白定量有显著差异（P＜0.01）,说明造模成功;阳性组、分清化浊胶囊各剂量组均能显著降低尿蛋白（P＜0.01）。与模型组比较,分清化浊胶囊高、中剂量能升高TP、ALB水平（P＜0.01）。分清化浊胶囊高、中剂量对TG及TC有降低作用（P＜0.01）。各治疗组对肾功能指标BUN、Cr无明显影响。各治疗组肾脏病变程度较模型组有明显减轻。结论 分清化浊胶囊可以显著降低阿霉素肾病大鼠尿蛋白、TC、TG;明显升高阿霉素肾病大鼠TP、ALB水平,减轻肾脏病理损害。     

白藜芦醇及SRT1720对2型糖尿病大鼠肾小球足细胞裂孔隔膜分子表达的影响

摘要：目的 研究白藜芦醇和SIRT1激活剂SRT1720对糖尿病大鼠肾功能以及足细胞损伤的干预作用,探讨SIRT1活化改善肾损害的作用和机制。方法 采用高脂饮食联合单侧肾切除和链脲佐菌素诱导方法建立2型糖尿病大鼠模型,用白藜芦醇和SRT1720等进行干预治疗。留取血清和肾脏,分析肾重及肾重/体重,检测空腹血糖、血肌酐、尿素氮等,采用免疫组化、逆转录-实时荧光定量PCR技术检测肾皮质中足细胞裂孔隔膜分子Nephrin和Podocin等蛋白原位表达和基因表达水平。结果 与正常组相比,模型组大鼠单侧肾重及肾重/体重比显著增高,空腹血糖、血肌酐和尿素氮均显著增高,肾皮质中Nephrin和Podocin蛋白表达和基因表达丰度显著降低。白藜芦醇和SRT1720治疗组各项检测指标均较模型组有所改善,白藜芦醇组肾重/体重指数、空腹血糖、Nephrin和Podocin表达等与模型组有统计学差异,SRT1720组空腹血糖、血肌酐、尿素氮、Nephrin和Podocin表达等与模型组均有统计学差异。结论 白藜芦醇、SRT1720 等SIRT1激活剂可显著改善糖尿病大鼠肾功能和足细胞损伤,在糖尿病肾病的防治方面具有重要价值和应用前途。 关键词：糖尿病肾病;白藜芦醇;SRT1720;Nephrin;Podocin     

大麻素受体1拮抗药类似物AM251对糖尿病肾病模型大鼠肾组织足细胞损伤的保护作用研究

目的：研究大麻素受体1（CB1）拮抗药类似物AM251对糖尿病肾病模型大鼠肾组织足细胞损伤的保护作用。方法：将大鼠随机分为阴性对照（生理盐水）组、对照[1mg／（kg·d）AM251】组、模型组和AM25l干预[建模＋1mg／（kg·d）AM251]组,每组10只。后2组建立糖尿病肾病模型,建模成功后腹腔注射相应药物,12周后检测各组大鼠24h尿蛋白量、血肌酐清除率（Ccr）、肾质量／体质量（KW／BW）、血清生化指标和肾组织中CBl和肾组织足细胞裂隙蛋白Nephrin、Podocin蛋白的表达,并观察肾组织和足细胞病理变化。结果：与阴性对照组比较,对照组大鼠各检测指标差异无统计学意义（P〉0．05）,模型组和AM251干预组大鼠24h尿蛋白量、KW／BW、血清生化指标和肾组织中CBl表达均明显增加（P〈0．05）,Ccr和足细胞中Nephrin、Podocin蛋白表达均明显降低（P〈0．05）;与模型组比较,AM25l干预组大鼠24h尿蛋白量、KW／BW明显降低（P〈0．05）,Ccr和足细胞中Nephrin、Podocin蛋白表达均明显增强（P〈0．05）,其余组间差异无统计学意义（P〉0．05）。阴性对照组和对照组大鼠肾组织和足细胞形态正常,模型组大鼠肾组织和足细胞有明显糖尿病肾病的病理改变,AM251干预组大鼠糖尿病肾病的病理改变较模型组均改善。结论：AM251对糖尿病肾病模型大鼠足细胞病变具有保护作用,部分机制可能与上调足细胞中Nephrin、Podocin蛋白的表达有关。     

脂必泰联合辛伐他汀对肾病综合征患者高脂血症的疗效

目的观察脂必泰联合辛伐他汀对肾病综合征患者高脂血症的疗效。方法 30例肾病综合征患者随机分为辛伐他汀组(对照组,14例)和辛伐他汀联合脂必泰组(联合组,16例),治疗前后分别检测两组患者血浆蛋白、血脂、24 h尿蛋白。结果两组治疗8周后血脂均明显下降(P<0.05),血浆白蛋白明显升高(P<0.05),尿白蛋白显著下降(P<0.05)。与对照组相比,联合组血脂及尿蛋白下降更多(P<0.05);血浆蛋白升高程度高于对照组(P<0.05)。结论脂必泰联合辛伐他汀能明显降低肾病综合征患者血脂水平和尿蛋白,升高血浆蛋白,疗效优于单独应用辛伐他汀。     

分清化浊胶囊对阿霉素肾病大鼠的影响

目的观察分清化浊胶囊对阿霉素肾病大鼠的影响及其可能的作用机制。方法将雄性SD大鼠随机分为6组（对照组,模型组,阳性对照组,分清化浊胶囊低、中、高剂量组）,除对照组外,其余各组大鼠采用尾iv阿霉素法制成阿霉素肾病大鼠模型,第一次尾iv阿霉素（4mg/kg）1周后,第二次iv阿霉素（3.5mg/kg）。造模成功后,对照组和模型组ig生理盐水,阳性对照组ig黄葵胶囊混悬液;其余治疗组ig分清化浊胶囊混悬液。每日一次,疗程4周。观察大鼠一般情况,在给药前、给药7、14、21、28d测定24h尿蛋白定量,末次给药后,测定大鼠血清总蛋白（TP）、白蛋白（ALB）、总胆固醇（TC）、三酰甘油（TG）、血尿素氮（BUN）、肌酐（Cr）,并观察大鼠肾脏病理变化。结果治疗前,与对照组比较,各治疗组尿蛋白定量有显著差异（P〈0.01）,说明造模成功;阳性组、分清化浊胶囊各剂量组均能显著降低尿蛋白（P〈0.01）。与模型组比较,分清化浊胶囊高、中剂量能升高TP、ALB水平（P〈0.01）。分清化浊胶囊高、中剂量对TG及TC有降低作用（P〈0.01）。各治疗组对肾功能指标BUN、Cr无明显影响。各治疗组肾脏病变程度较模型组有明显减轻。结论分清化浊胶囊可以显著降低阿霉素肾病大鼠尿蛋白、TC、TG;明显升高阿霉素肾病大鼠TP、ALB水平,减轻肾脏病理损害。     

白藜芦醇对膜性肾病大鼠的肾保护作用

目的研究白藜芦醇对膜性肾病大鼠的肾保护作用及可能的作用机制。方法将SD大鼠随机分为正常组、模型组及实验组,各20只。用尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建膜性肾病大鼠,正常组给予等量生理盐水。建模后实验组灌胃白藜芦醇(30 mg·kg-1),模型组及正常组灌胃等量生理盐水,每天1次,连续干预4周。用分光光度计检测24 h尿蛋白定量(UTP),用试剂盒检测血清中肌酸酐(Scr)、尿素氮(BUN)、白蛋白(ALB)、总胆固醇(TC)指标水平,以免疫组化法检测大鼠肾组织synaptopodin蛋白表达情况,以蛋白质印迹(WB)法检测大鼠肾组织中p-Akt、mTOR、PI3K蛋白表达。结果正常组、模型组和实验组大鼠血清中Scr分别为(29.16±1.77),(52.64±2.78)和(40.55±2.65)μmol·L^-1,BUN分别为(5.86±1.35),(13.54±2.36)和(7.66±3.45)mmol·L^-1,24 h UTP分别为(6.85±1.26),(39.52±1.24)和(25.36±1.42)mg,ALB分别为(32.15±3.49),(19.63±2.48)和(26.34±2.58)g·L^-1,TC分别为(1.26±0.52),(4.02±0.36)和(2.36±0.52)mmol·L^-1,肾组织synaptopodin蛋白表达量分别为(45.36±2.18)%,(12.63±3.85)%,(23.26±3.09)%,差异均有统计学意义(均P<0.05)。模型组肾组织中磷酸化蛋白激酶B(p-Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)、磷脂酰肌醇3-激酶(PI3K)相对表达量较正常组升高,而实验组低于模型组,差异均有统计学意义(均P<0.05)。结论白藜芦醇可减少膜性肾病大鼠尿蛋白程度,防止synaptopodin降解,降低PI3K/Akt/mTOR信号通路中蛋白表达,从而发挥对膜性肾病的肾保护作用。     

芪龙通肾方治疗膜性肾病大鼠蛋白尿的作用机制研究

目的观察芪龙通肾方治疗膜性肾病大鼠蛋白尿的疗效及作用机制。方法将SD大鼠随机分为空白,模型,阳性(雷公藤多苷片),芪龙通肾汤低、中、高剂量组,采用隔日1次尾静脉注射阳离子化牛血清白蛋白(C-BSA)方法复制膜性肾病大鼠模型,各组连续腹腔内注射治疗4周后检测大鼠尿蛋白定量(24 h)及血清指标[总蛋白(TP)、白蛋白(ALB)、血清总胆固醇(TC)、甘油三酯(TG)、尿素氮(BUN)、肌酐(Scr)、转化生长因子(TGF)-β1],采用光镜及电镜观察肾脏病理学改变。结果与模型组比较:阳性及芪龙通肾汤低、中、高剂量组尿蛋白定量(24 h)明显降低(P<0.05),且芪龙通肾汤中、高剂量明显低于阳性组(P<0.05);阳性及芪龙通肾汤高剂量组对血清TP、TC明显降低(P<0.05);阳性、芪龙通肾汤低、中、高剂量组对血清ALB明显升高、对TG和TGF-β1明显降低(P<0.05)。光镜及电镜观察,治疗组在肾小球基底膜免疫复合物沉积、基底膜增厚及足突融合等方面较模型组明显减轻。结论芪龙通肾方能有效降低膜性肾病大鼠蛋白尿,提高血清白蛋白,降低TGF-β1水平,减轻肾脏病理损伤。