Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence-accelerated mouse

At 8 weeks after intragastric administration of icariin to senescence-accelerated mice （P8 strain）, Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected significantly increased levels of cyclic adenosine monophosphate response element binding protein These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippocampus of the senescence-accelerated mouse.

EFFECT OF ORIENTATION ON STRESS RESPONSE,FRICTION STRESS AND BACK STRESS DURING CYCLIC DEFORMATION IN Al SINGLE CRYSTALS

The symmetrical push-pull fatigue tests at strain amplitude of 2×10~3 with different slip orientation of Al single crystals,were carried out at room temperature in air.The peak stresses of various cycles were measured and the stress-strain hysteresis loops for selected cy- cles were recorded.The energy losses.friction stresses,back stresses and shape

EFFECT OF SLIP ORIENTATION ON STRESS RESPONSE,INTERNAL FRICTION AND ULTRASONIC ATTENUATION DURING CYCLIC DEFORMATION IN Al SINGLE CRYSTALS

The variation of cyclic stress,internal friction and ultrasonic attenuation during cyclic deformation and relations among them have been investigated with different slip orientation Al single crystals.The results indicate that the value of cyclic stress σ,internal friction Q^(-1)and ultrasonic attenuation △α depend obviously on the slip orientation.There are large differences in above three parameters for different slip orientation Al crystals.In early stage of fatigue life,σ and △α increase and Q^(-1)decreases with cycles N,and △α reached maxi- mum before σ,while Q^(-1)and σ get the valley and the peak,respectively,at same cycles.

INFLUENCE OF TEMPERATURE-DEPENDENT PROPERTIES ON TEMPERATURE RESPONSE AND OPTIMUM DESIGN OF C/M FGMS UNDER THERMAL CYCLIC LOADING

The influence of temperature-dependent properties on temperature response and optimum design of newly developed ceramic-metal functionally graded materials under cyclic thermal loading and high temperature gradient environment is studied. The thermal conductivity of the material is considered to be dependent on the temperature. In this paper, the temperature response of the material is calculated using a nonlinear finite element method. Emphasis is placed on the influence of temperatue-dependent properties on the thermal response and insulation property of the material render the different graded compositional distributions and different heat flux magnitudes. Through the analysis, it is suggested that the influence of temperature-dependent properties can not be neglected in the temperature response analysis and the optimum design process of the material must be based on the temperature-dependent temperature analysis theory.

Cyclic Voltammetric Responses of Nitrate Reductase on Chemical Modified Electrodes

Electrochemistry of nitrate reductases (NR) incorporated into 2-aminoethanethiol self-assembled on the gold electrode and polyacrylamide cast on the pyrolytic graphite electrode was examined. NR on chemical modified electrode showed electrochemical cyclic voltammetric responses in phosphate buffers.

Sevoflurane effects on cyclic adenosine monophosphate response element binding protein,phosphorylated cyclic adenosine monophosphate response element binding protein,and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat

BACKGROUND： Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE： To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein （CREB）, phosphorylated CREB （pCREB）, and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS： Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS： A total of 42 female, Wistar rats were randomly assigned to the following groups： sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES： CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS： CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group （P 〈 0.01）. However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group （P 〈 0.01）. Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group （P 〈 0.01）. Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION： Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.

INFLUENCE OF TEMPERATURE-DEPENDENT PROPERTIES ON THERMAL STRESSES RESPONSE AND OPTIMUM DESIGN OF C/M FGMS UNDER THERMAL CYCLIC LOADING

The influence of temperature-dependent properties on thermal stresses response and optimum design of newly developed ceramic-metal functionally graded materials under cyclic thermal loaning and high temperature gradient environment is studied. The thermal conductivity of material is considered to be dependent on the temperature. In this paper, the thermal stresses response of the material is calculated rising a nonlinear finite element method. Emphasis is placed on the influence of temperature-dependent properties on the thermal stresses response characteristics, the thermal stresses relaxation property and the thermal stresses history under the different graded compositional distributions and different heat flux magnitudes. Through tile analysis. it is suggested that the influence of temperature-dependent properties can not be neglected In the thermal stresses response analysis and the optimum design process of the material must be based on the temperature-dependent thermo-elastic-plastic theory.

THERMO-ELASTIC-PLASTIC RESPONSE AND OPTIMUM DESIGN OF CERAMIC-METAL FGMS-CYCLIC THERML LOADING PROBLEM

The materials are made with a graded composition and microstructure in the thickness direction from the ceramic side to the metal side. The cyclic thermal loading and high temperasure gradient environment are simulated by heating the ceramic surface with a cyclic hear flux input and cooling the metal surface with a flowing liquid niterogen. The thermal and themo-elastic-plastic response of the materials is calculated using the isotropic hardening model and kinetic hardening model. Emphasis is placed on the response analysis under the different graded compositional distributions. Through the response analysis, the optimum design process of the graded composition under the dynamic case is established, which is bused on a unified viewpoint of the heat insulation property, thermal stress relaxation property and stress history feature.

Evidences for involvement of endogenous cAMP in Arabidopsis defense responses to Verticillium toxins

Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades, there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical “wilt” symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway. Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endog- enous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticillium- secreted toxins by regulating the production of the known signal SA in plant defense pathway.

Modelling spiky acceleration response of dilative sand deposits during earthquakes with emphasis on large post-liquefaction deformation

The acceleration records at some liquefied sand deposits exhibit a distinctive spiky waveform, characterized by strong amplification and high-frequency components. A comprehensive constitutive model was used to analyze the mechanism of such spiky acceleration responses. An idealized single-degree-of-freedom（SDF） system was constructed, in which the force-displacement relation of the spring follows the stress-strain behavior of saturated sand during undrained shearing. The SDF system demonstrated that the spikes are directly related to the strain-hardening behavior of sand during post-liquefaction cyclic shearing. Furthermore, there exists a threshold shear strain length, which is in accordance with the limited amplitude of the fluid-like shear strain generated at instantaneous zero effective stress state during the post-liquefaction stage. The spiky acceleration can only occur when the cyclic shear strain exceeds the threshold shear strain length. It is also revealed that the time intervals between the acceleration spikes increase gradually along with the continuation of shaking because the threshold shear strain length increases gradually and then more time is needed to generate larger shear strain to cause strain hardening. Records at the Kushiro Port site and Port Island site during past earthquakes are simulated through the fully coupled method to validate the presented mechanism.

山姜素调节cAMP/PKA/CREB信号通路促进骨质疏松性骨折大鼠骨折愈合

背景:山姜素具有抗炎、抗肿瘤、抗菌等作用,已被证实能够缓解骨质疏松症,但山姜素对骨质疏松性骨折的影响及机制仍不清楚。目的:探讨山姜素调节环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白信号通路对骨质疏松性骨折大鼠的改善作用。方法:采用双侧卵巢切除手术构建骨质疏松症骨折大鼠模型,将成功造模大鼠依据随机数字表法分为山姜素低、中、高剂量组、抑制剂组和模型组,另选12只大鼠作为假手术组。骨折造模当天,山姜素低、中、高剂量组大鼠灌胃7.5,15,30 mg/kg的山姜素+腹腔注射等量的生理盐水,抑制剂组灌胃30 mg/kg的山姜素+腹腔注射5 mg/kg的H-89(通路抑制剂),模型组与假手术组给予(灌胃+腹腔注射)等量生理盐水,1次/d,连续8周。放射性检查评估大鼠骨折愈合情况并进行愈合评分;骨密度扫描仪测定骨折处骨密度;通过三点弯曲实验和压缩实验评估大鼠股骨生物力学状况;苏木精-伊红染色观察大鼠骨折处病理损伤;酶联免疫吸附(ELISA)法检测血清碱性磷酸酶、骨钙素和Ⅰ型胶原交联C-末端肽、环磷酸腺苷水平的变化;Western blot检测股骨组织中骨形态发生蛋白2和环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白通路蛋白表达。结果与结论:①相较于假手术组,模型组大鼠骨折愈合评分、骨密度、最大负荷、最大应力、碱性磷酸酶、骨钙素、环磷酸腺苷水平、骨形态发生蛋白2、磷酸化蛋白激酶A/蛋白激酶A、磷酸化环磷酸腺苷反应元件结合蛋白/环磷酸腺苷反应元件结合蛋白表达下降,Ⅰ型胶原交联羧基末端肽水平增加(P<0.05);与模型组比较,山姜素各剂量组大鼠上述各项指标呈现相反的变化(P<0.05);与山姜素高剂量组比较,抑制剂组大鼠上述指标变化均被逆转(P<0.05)。②结论:山姜素可能通过激活环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白信号通路加速骨质疏松症骨折大鼠的骨折愈合。

Numerical modeling of centrifuge cyclic lateral pile load experiments

To gain insight into the inelastic behavior of piles, the response of a vertical pile embedded in dry sand and subjected to cyclic lateral loading was studied experimentally in centrifuge tests conducted in Laboratoire Central des Ponts et Chaussees. Three types of cyclic loading were applied, two asymmetric and one symmetric with respect to the unloaded pile. An approximately square-root variation of soil stiffness with depth was obtained from indirect in-flight density measurements, laboratory tests on reconstituted samples, and well-established empirical correlations. The tests were simulated using a cyclic nonlinear Winkler spring model, which describes the full range of inelastic phenomena, including separation and re-attachment of the pile from and to the soil. The model consists of three mathematical expressions capable of reproducing a wide variety of monotonic and cyclic experimentalp-y curves. The physical meaning of key model parameters is graphically explained and related to soil behavior. Comparisons with the centrifuge test results demonstrate the general validity of the model and its ability to capture several features of pile-soil interaction, including： soil plastification at an early stage of loading, ＂pinching＂ behavior due to the formation of a relaxation zone around the upper part of the pile, and stiffness and strength changes due to cyclic loading. A comparison of the p-y curves derived from the test results and the proposed model, as well as those from the classical curves of Reese et al. （1974） for sand, is also presented.

Modeling and cyclic behavior of segmental bridge column connected with shape memory alloy bars

This paper examines the quasi-static cyclic behavior, lateral strength and equivalent damping capacities of a system of post-tensioned segmental bridge columns tied with large diameter martensitic Shape Memory Alloy （SMA） link-bars. Moment-curvature constitutive relationships are formulated and analysis tools are developed for the PT column, including a modified four-spring model prepared for the SMA bars. The suggested system is exemplified using a column with an aspect ratio of 7.5 and twelve 36.5 mm diameter NiTi martensitic SMA bars. A post-tensioning force of 40% to 60% of the tendon yield strength is applied in order to obtain a self re-centering system, considering the residual stress of the martensitie SMA bars. The cyclic response results show that the lateral strength remains consistently around 10% of the total vertical load and the equivalent viscous damping ratios reach 10%-12% of critical. When large diameter NiTi superelastic SMA bars are incorporated into the column system, the cyclic response varies substantially. The creep behavior of the superelastic SMA bar is accounted for since it affects the re-centering capability of the column. Two examples are presented to emphasize the modeling sensitivities for these special bars and quantify their cyclic behavior effects within the column assembly.

Development and subassemblage cyclic testing of hybrid buckling-restrained steel braces

Buckling-restrained braced frames(BRBFs) are vulnerable to relatively higher post-earthquake residual drifts under high intensity ground shakings. This is primarily due to the low axial elastic and post-elastic stiffness of bucklingrestrained braces(BRBs) satisfying the design force demand requirements. In the present study, a hybrid buckling restrained bracing system consisting of a short yielding core length BRB component and a conventional buckling-type brace component connected in series has been developed with an aim to increase the axial stiffness of braces. This study is focused on the experimental investigation of six hybrid bucking restrained braces(HBRBs) to investigate their overall behavior, loadresisting capacity, strength-adjustment factors and energy dissipation potential. The main parameters varied are the crosssectional area, the yielding length of core elements as well as the detailing of buckling-restraining system of short yielding core length BRBs. Test results showed that the HBRBs with yielding core length in the range of 30% of work-point to workpoint lengths withstood an axial strain of 6% without any instability and can deliver stable and balanced hysteretic response and excellent energy dissipation under reversed cyclic loading conditions.

Experimental study of seismic cyclic loading effects on small strain shear modulus of saturated sands

The seismic loading on saturated soil deposits induces a decrease in effective stress and a rearrangement of the soil-particle structure, which may both lead to a degradation in undrained stiffness and strength of soils. Only the effective stress influence on small strain shear modulus Gmax is considered in seismic response analysis nowadays, and the cyclic shearing induced fabric changes of the soil-particle structure are neglected. In this paper, undrained cyclic triaxial tests were conducted on saturated sands with the shear wave velocity measured by bender element, to study the influences of seismic loading on Gmax. And Gmax of samples without cyclic loading effects was also investigated for comparison. The test results indicated that Gmax under cyclic loading effects is lower than that without such effects at the same effective stress, and also well correlated with the effective stress variation. Hence it is necessary to reinvestigate the determination of Gmax in seismic response analysis carefully to predict the ground responses during earthquake more reasonably.

Cyclic deformation behaviors of Ti-46Al-2Cr-2Nb-0.15B alloy during thermo-mechanical fatigue tests

Thermo-mechanical fatigue tests were carried out on the gamma-TiAl alloy in the temperature range of 500-800℃ under mechanical strain control m order to evaluate its cyclic deformation behaviors at elevated temperature. Cyclic deformation curves, stress-strain hysteresis loops under different temperature--strain cycles were analyzed and dislocation configurations were also observed by TEM. The mechanisms of cyclic hardening or softening during thermo-mechanical fatigue （TMF） tests were also discussed. Results showed that thermo-mechanical fatigue lives largely depended on the applied mechanical strain amplitudes, applied types of strain and temperature. On the hysteresis loops appeared two apparent asymmetries： one was zero asymmetry and the other was tensile and compressive asymmetry. Dislocations configuration and slip behaviors were contributed to cyclic hardening or cyclic softening.

黄芩苷调节cAMP/PKA/CREB信号通路对湿疹大鼠皮肤屏障功能的影响

目的探讨黄芩苷(BA)调节环磷酸腺苷(cAMP)/蛋白激酶A(PKA)/cAMP反应元件结合蛋白(CREB)通路对湿疹大鼠皮肤屏障功能的影响。方法将SD大鼠随机分为对照组(NC组)、Model组、低剂量BA组(BA-L组,25 mg/kg)、中剂量BA组(BA-M组,50 mg/kg)、高剂量BA组(BA-H组,100 mg/kg)、泼尼松组(PNS组,25 mg/kg)、BAH+cAMP抑制剂(SQ22536)组(100 mg/kg+2.13 mg/kg)、BA-H+PKA抑制剂(H-89)组(100 mg/kg+5 mg/kg),每组12只。除NC组外,其余组大鼠均构建湿疹大鼠模型。建模成功2 d后,分组进行给药处理。检测湿疹面积及严重度指数(EASI)评分、经皮肤水分流失量(TEWL)、角质层含水量(WCSC)变化;酶联免疫吸附试验(ELISA)检测大鼠血清中免疫球蛋白E(IgE)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)水平及大鼠背部受试区皮损组织中c AMP蛋白表达;HE染色检测大鼠背部受试区皮损组织病理变化;Western blot检测大鼠背部受试区皮损组织中水通道蛋白3(AQP3)、cathelicidin相关抗菌肽(CRAMP)、p-PKA、p-CREB蛋白表达。结果与NC组比较,Model组大鼠背部受试区皮损组织病理损伤严重,EASI评分、TEWL、IgE、IL-4水平升高,WCSC、IFN-γ水平、AQP3、CRAMP、cAMP、p-PKA、p-CREB蛋白水平降低(P<0.05)。与Model组比较,BA-L组、BA-M组、BA-H组、PNS组大鼠背部受试区皮损组织病理损伤减轻,EASI评分、TEWL、IgE、IL-4水平降低,WCSC、IFN-γ水平、AQP3、CRAMP、cAMP、p-PKA、p-CREB蛋白水平升高(P<0.05);且BA-L组、BA-M组、BA-H组上述指标变化呈剂量依赖性。SQ22536或H-89减弱了高剂量BA对湿疹大鼠皮肤屏障功能的改善作用。结论BA可能通过激活cAMP/PKA/CREB信号通路改善湿疹大鼠皮肤屏障功能。

淫羊藿苷调控mTOR/Akt/CREB通路对高糖诱导的足细胞自噬及凋亡的影响

目的 探讨淫羊藿苷对高糖诱导的足细胞自噬、凋亡及哺乳动物雷帕霉素靶蛋白(mTOR)/丝氨酸苏氨酸蛋白激酶(Akt)/环磷酸腺苷反应元件结合蛋白(CREB)通路的影响。方法 将小鼠足细胞MPC5分为5组:正常对照组(5.5 mmol·L^(-1)葡萄糖)、高糖组(30 mmol·L^(-1)葡萄糖)、淫羊藿苷组(30 mmol·L^(-1)葡萄糖+5μmol·L^(-1)淫羊藿苷)、GDC-0349组(30 mmol·L^(-1)葡萄糖+50μmol·L^(-1)GDC-0349)、淫羊藿苷+GDC-0349组(30 mmol·L^(-1)葡萄糖+5μmol·L^(-1)淫羊藿苷+50μmol·L^(-1)GDC-0349)。培养48 h后,噻唑蓝法检测MPC5细胞活力;吖啶橙染色观察MPC5细胞自噬情况;流式细胞术检测MPC5细胞凋亡;蛋白印迹法检测MPC5细胞自噬[微管相关蛋白1轻链3(LC3)Ⅱ、LC3Ⅰ、自噬相关蛋白(Beclin-1)]、凋亡[Bcl-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)]和mTOR/Akt/CREB通路相关蛋白的表达。结果 与正常对照组比较,高糖组MPC5细胞活力、Bcl-2、磷酸化mTOR(p-mTOR)/mTOR、磷酸化Akt(p-Akt)/Akt、磷酸化CREB(p-CREB)/CREB蛋白表达水平显著降低(P<0.05),自噬能力增强,自噬体表现出橙色荧光,细胞凋亡率、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bax蛋白表达水平显著升高(P<0.05)。与高糖组比较,淫羊藿苷组MPC5细胞活力、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bcl-2、p-mTOR/mTOR、p-Akt/Akt、p-CREB/CREB蛋白表达水平显著升高,自噬能力进一步增强,自噬体数量增多,自噬体呈现出砖红色荧光(P<0.05),细胞凋亡率、Bax蛋白表达水平显著降低(P<0.05);GDC-0349组MPC5细胞活力、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bcl-2、p-mTOR/mTOR、p-Akt/Akt、p-CREB/CREB蛋白表达水平显著降低,自噬能力减弱,自噬体数量减少,自噬体表现出橙色荧光(P<0.05),细胞凋亡率、Bax蛋白表达水平显著升高(P<0.05);淫羊藿苷+GDC-0349可逆转淫羊藿苷对高糖诱导MPC5细胞的作用效果(P<0.05)。结论 淫羊藿苷通过激活mTOR/Akt/CREB通路促进高糖诱导的足细胞自噬抑制细胞凋亡。

国产低屈服点芯材屈曲约束支撑的滞回性能及减震效果研究

为了研究芯材为LY160软钢的屈曲约束支撑滞回性能以及减震效果,针对LY160钢材和BRB构件进行了从材性、构件性能、到结构地震响应的系统试验和分析工作。首先完成了LY160钢材的材性试验,得到LY160钢材试件的平均屈服强度为170MPa,断裂伸长率为48.2%;随后进行了屈曲约束支撑的低周往复加载试验,采用LY160的屈曲约束支撑破坏位移为1/45L,延性系数达到17,最后开展了6层钢筋混凝土框架结构的弹塑性地震响应分析,发现使用LY160芯材的LBRB结构相较于使用Q235芯材的普通NBRB结构,不仅结构动力响应的减震效果提升了25%,同时还可有效地改善结构在强震下的塑性损伤,采用低屈服点软钢为芯板的屈曲约束支撑可以有效提升结构的抗震安全性。

红景天苷改善顺铂引起的小鼠耳蜗毛细胞和螺旋神经节神经元损伤的机制

目的探究红景天苷(SAL)改善顺铂(CIS)引起的耳蜗毛细胞(CHC)和螺旋神经节神经元(SGN)损伤的作用及其与环磷腺苷(cAMP)/蛋白激酶A(PKA)/cAMP效应元件结合蛋白(CREB)通路的关系。方法分离新生C57BL/6小鼠的耳蜗基底膜,分为对照组(C组)、CIS组、SAL组、SAL+SQ22536(cAMP抑制剂)组和SAL+H-89(PKA抑制剂)组,每组20条。C组仅加入无血清BME培养液;CIS组在培养液中加入15μmol/L CIS;SAL组在CIS组基础上加入5μmol/L SAL;SAL+SQ22536组在CIS组基础上加入5μmol/L SAL和5μmol/L SQ22536;SAL+H-89组在CIS组基础上加入5μmol/L SAL和30μmol/L H-89。各组在培养箱中孵育48 h后,免疫荧光染色观察各组CHC和SGN损伤;试剂盒检测各组耳蜗基底膜中ROS和cAMP含量;Western blot检测各组PKA、p-CREB、CREB、Bcl-2、BDNF、NF-M蛋白水平。结果CIS组CHC排列混乱、体积肿大,SGN细胞核破碎、神经突缺失,SAL可减轻CHC和SGNs损伤。与C组相比,CIS组CHC、SGN数量较少(P<0.05),ROS、cAMP含量、PKA、BDNF、NF-M、Bcl-2蛋白及p-CREB/CREB水平较高(P<0.05);与CIS组相比,SAL组CHC、SGN数量较多(P<0.05),ROS含量较低(P<0.05),cAMP含量、PKA、BDNF、NF-M、Bcl-2蛋白及p-CREB/CREB水平较高(P<0.05)。SQ22536和H-89均可逆转SAL对CHC和SGN的保护作用。结论SAL可能通过激活cAMP/PKA/CREB通路,促进抗凋亡蛋白和神经保护因子表达,缓解CIS引起的CHC和SGN损伤。