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??OBJECTIVE To investigate the effect of ??-secretase inhibitor DAPT in inflammation-induced brain white matter injury in neonatal mice.METHODS Sixty C57BL/10J neonatal mice are randomly divided into control group, control+DAPT (10 mg??kg^-1) group, inflammation (LPS) group, LPS+DAPT group (inflammation exposure after 10 mg??kg^-1 DAPT treatment). All neonatal mice were killed and brain was removed to the following observation and detection:at P5, the mRNA expression variation of IL-1??, IL-8,TNF-??,Hes1 and NICD by Real-time PCR methods. Oligodendrocytes were identified by immunofluorescence staining. Myelin basic protein (MBP) protein expression was detected by Western blot assay.RESULTS LPS group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expression of IL-1??, IL-8, TNF-??, Hes1 and NICD between LPS+DAPT group and LPS group (P<0.05), and the mRNA expression of IL-1??, IL-8,TNF-??,Hes1 and NICD in inflammation-treated were significantly increased than control group (P<0.05). The results showed more expression of MBP in LPS+DAPT group compared with LPS group (P<0.05). Compared with the blank control group, which was obviously decreased after 48 h of inflammation (P<0.05).CONCLUSION Inflammation leads to abnormal of notch signal expression in neonatal mice, and which is shows inflammation involved in brain damage.Its mechanism is probably associated with the maturation of oligodendrocytes.     

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??OBJECTIVE To investigate the protective effect and possible mechanism of Rhizoma Coptis(RC) on lipopolysaccharide(LPS)-induced inflammatory injury in rat hepatocytes(BRL). METHODS LPS-induced BRL cells injury model was established in vitro, then the damaged cells were given different interventions and treatment with 0.175, 0.1 mg?? mL^-1 RC aqueous extract as the test drug, and dexamethasone(Dex) as positive control drug. The optimal test doses of LPS and RC aqueous extract were selected and determined by cell counting kit-8(CCK-8), the cellular apoptosis rate was determined by flow cytometry, TLR4/NF-??B and TLR4/IRF3 signaling pathways and the mRNA level of related inflammatory mediators(TNF-??, IL-1??, IL-6) were detected by RT-PCR, the NF-??B p65 protein expression was analysed by Western blot and immunofluorescence techniques. RESULTS ??Compared with normal control group, 0.1 mg??mL^-1 LPS affected on BRL cells for 24 h, the cell survival rate was decreased significantly(P<0.01), the apoptotic rate increased significantly(P<0.01), the mRNA level of TLR4, NF-??B, IRF3, TNF-??, IL-1??, IL-6 were significantly increased(P<0.01), and the NF-??B p65 protein expression was increased. ??Compared with the model group, 0.1 and 0.175 mg??mL^-1 RC affected on LPS-induced BRL cells for 24 h, the survival rate of BRL cells was increased significantly(P<0.05), the apoptotic rate decreased significantly(P<0.01), the mRNA level of TLR4, NF-??B, IRF3, TNF-??, IL-1??, IL-6 and the NF-??B p65 protein expression were decreased significantly(P<0.01). CONCLUSION Rhizoma Coptis has obviously protective effect on LPS-induced inflammatory injury in rat hepatocytes(BRL), the mechanism of which may be related with inhibiting apoptosis, reducing the release of inflammatory factors such as TNF-????IL-1?? and IL-6, blocking NF-??B p65 protein nuclear translocation, interfering the R4/NF-??B and TLR4/IRF3 signaling pathway.     

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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.     

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??OBJECTIVE To observe the effect of chlorogenic acid on the secretion of inflammatory cytokines and regulation mechanism of P38MAPK, NF-??B signaling pathway in human hepatic stellate cells induced by TGF-??1. METHODS Different concentrations of CGA worked in normal and activated hepatic stellate cells to make sure the appropriate drug concentration.The exponential growth phase cells were randomly divided into normal HSC group, normal HSC+CGA group, after cultured 48 h, the cells were cultured with 0??50??100 mg??L^-1 CGA for 24 h; HSC(TGF-??1) group?? HSC(TGF-??1 + CGA) group: after 24 h, the cells were induced by 10 ??g??L^-1 TGF-??1 for 24 h, and then cultured with 0, 50, 100 mg??L^-1 CGA for 24 h. The expression of ??-SMA protein was detected by immunocytochemistry, the expression of p-P38, P65 protein was detected by Western-blot, the expression of TNF-??, IL-6 mRNA was detected by real time quantitative PCR, and the content of TNF-??, IL-6 in the supernatant was detected by ELISA method. RESULTS The appropriate concentrations of CGA were 50 and 100 mg??L^-1, these concentration has no effect on normal HSC(P>0.05); after stimulation by TGF-??1, the expression of ??-SMA, p-P38, P65, TNF-??, IL-6 was increased(P<0.01), when activated HSC cells were treated with 50 and 100 mg??L^-1 CGA, the expression of ??-SMA, p-P38, P65, TNF-??, IL-6 was decreased(P<0.05, P<0.01). CONCLUSION CGA can inhibit the proliferation of activated HSC, regulate the secretion of inflammatory factors such as TNF-??, IL-6 by P38MAPK and NF-??B signaling pathway, inhibit the occurrence of liver fibrosis.     

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??OBJECTIVE To study the effect of kangfuxin on damp-heat syndrome combined with TNBS-induced ulcerative colitis in rats and to explore its mechanism. METHODS Rat model of damp-heat was established by high-fat and high-sugar diet, and then combined with TNBS to establish rat model of damp-heat, respectively, to give sulfasalazine, rehabilitation, high, medium and low dose enema, by measuring disease activity index(DAI), colonic mucosal injury index(CMDI) and histopathological score(HS). The levels of IL-8, IL-17 and IL-2, MPO, EGF and TNF-?? in serum were measured by enzyme-linked immunosorbent assay(ELISA). RESULTS Compared with the model control group, the high dose group can significantly reduce the DAI, HS and CMDI scores of the damp-heat type UC rats(P<0.01, P<0.05). Each group type can reduce the heat UC rat serum IL-8, IL-17 and expression of MPO,TNF-?? in colon tissue, increases, the expression of rat IL-2 EGF(P<0.01). CONCLUSION Kangfuxin has a certain therapeutic effect on damp-heat type UC rats, and its mechanism may be related to down-regulating the expression of IL-8, IL-17,MPO and TNF-??, up-regulating the expression of IL-2 and EGF.     

五味子醇甲对APP/PS1小鼠学习记忆和NF-κB p65的影响

目的研究五味子醇甲(SCH)对APP/PS1双转基因痴呆小鼠行为学和NF-κB p65的影响。方法将35只APP/PS1双转基因痴呆小鼠随机分为模型(APP/PS1)组、五味子醇甲(SCH+APP/PS1)组;另以同背景同月龄的C 57 BL/6 J阴性小鼠为空白(WT)组。SCH+APP/PS1组给予SCH悬浊液灌胃(2.6 mg·kg^-1·d^-1),模型组和空白组给予等量蒸馏水灌胃。各组灌胃30 d进行Mirror水迷宫空间探索试验后取材。HE染色法观察皮层及海马CA1区神经细胞的形态结构。运用DCFH-DA法检测脑组织活性氧(ROS)含量。Western印迹检测法检验磷酸化核转录因子(NF-κB p65,pp65)的表达。结果与APP/PS 1组相比,APP/PS 1+SCH组有效区停留距离及时间明显延长,差异有统计学意义(P<0.05,P<0.01);APP/PS 1+SCH组穿越有效区次数和平台区停留距离增加,均差异有统计学意义(P<0.01)。APP/PS 1+SCH组HE染色观察皮层有部分神经细胞萎缩、减少,较APP/PS1组明显好转,海马细胞排列整齐度尚可、较均匀。与APP/PS1组相比,APP/PS1+SCH组能降低ROS含量,差异有统计学意义(P<0.05)。APP/PS 1+SCH组皮层及海马pp65蛋白相对表达量下调(P<0.05,P<0.01)。结论SCH可能通过降低ROS含量和抑制pp65保护脑组织形态结构和提高APP/PS1鼠空间探索记忆能力。     

电针对APP/PS1小鼠行为学及大脑皮层Klotho基因表达的影响

本研究通过观察APP/PS1小鼠大脑皮层Klotho基因的表达及其空间学习记忆能力,探讨电针治疗阿尔兹海默病（AD）的机理。方法：APP/PS1双转基因小鼠,随机分为模型组、电针组（百会穴、印堂穴、人中穴）,以C57BL/6野生型小鼠作为对照组;采用Morris水迷宫进行空间记忆行为学测试,以免疫组化法观察皮层Klotho蛋白表达趋势,real-timePCR技术检测大脑皮层Klotho mRNA表达水平。结果：与对照组相比,模型组逃避潜伏时间增加、平台穿越次数、平台象限游泳路程减少;与模型组相比,电针组逃避潜伏时间明显减少。与正常组相比,模型组大脑皮层Klotho mRNA表达减少;与模型组相比,电针组Klotho mRNA表达增加。Real time PCR结果与免疫组化所示表达趋势一致。结论：电针可提高APP/PS1小鼠的空间记忆能力,其机制可能与上调Klotho mRNA表达有关。     

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??OBJECTIVE To study the effects of Kadsura coccinea alcohol extract(KCAE) on rats with immunologic hepatic fibrosis and research the possible mechanisms in it. METHODS Totally 60 SD male rats were randomly divided into 6 groups: a normal control group,a model group, a compound Biejia-ruangan tablets group(0.7 g??kg^-1), KCAE high, middle and low dose groups(1.68, 0.84, 0.42 g??kg^-1) at ten in each groups. Except for the normal control group,other groups were duplicated intraperitoneal injection of porcine serum twice a week at dose of 0.5 mL??time^-1. The rats in treatment groups were intragastric administration respectively, meanwhile, the rats in normal control and model groups were treated with the same volume of distilled water, once a day for 15 weeks. The liver was weighed to calculate the liver index. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), total protein(TP), albumin(ALB) and total bilirubin(TB) were evaluated by the Mind-Ray automatic biochaemical analyzer. The expression level of procollagen ??(PC??), collagen type ??(??-C), laminin(LN), hyaluronic acid(HA), transforming growth factor-??1(TGF-??1), interkeukin-10(IL-10), interferon-??(IFN-??) and tumor necrosis factor-??(TNF-??) in serum were detected by ELISA. The degrees of fibrosis were evaluated by HE and Masson straining, and the expression levels of TGF-??₁ in liver tissue were assessed by Western blot. RESULTS Compared with model group, the liver index of KCAE high-dose group was decreased significantly(P??0.01). The expression levels of ALT, AST, TP, ALB, TB were within normal range, the differences were not statistically significant(P>0.05). KCAE could decrease the level of PC??, IV-C, LN, HA, TGF-??₁, TNF-?? and increase the level of IFN-?? in serum. KCAE could alleviate the hepatic fibrosis in rats(P??0.01) and inhibit the expression of TGF-??₁ in the liver tissues significantly(P??0.01). CONCLUSION KCAE has an anti-immunologic hepatic fibrosis effect in rats and the mechanisms possibly involve effectively regulating inflammatory cytokines, reducing extracellular matrix expression and inhibiting the expression of TGF-??₁.