姜黄素预处理通过保护线粒体和抗氧化应激减轻干热环境热射病大鼠肝损伤

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目的:研究姜黄素预处理对干热环境热射病大鼠肝脏的保护作用及机制。方法:将50只SD大鼠随机分为5组(n=10):常温对照组(Control),干热对照组(HS),50-cur组,100-cur组和200-cur组。Control组、HS组给予生理盐水灌胃,50-cur组、100-cur组、200-cur组分别给予50 mg/kg、100 mg/kg、200 mg/kg浓度的姜黄素灌胃,每天1次,连续7天。第8天除Control组外,其余4组大鼠转移至西北特殊环境人工实验舱(环境温度41±0.5℃,湿度10±1%)进行实验。实验的第150分钟,检测肛温,麻醉后取材。同时Control组直接检测肛温并麻醉取材。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的含量和细胞色素C(Cyt-c)的表达情况。电镜观察肝细胞超微结构的变化。结果:(1)第150分钟,各组大鼠体温均超过42℃,达到热射病状态。姜黄素预处理组体温较HS组降低(P<0.01)。姜黄素预处理组组间差异无统计学意义(P>0.05)。(2)HS组ALT、AST水平较Control组升高(P<0.01)。姜黄素预处理组ALT、AST水平较HS组降低(P<0.05),姜黄素预处理组组间差异有统计学意义(P<0.05)。(3)HS组与Control组相比MDA水平升高,SOD、CAT水平降低(P<0.01)。姜黄素预处理组与HS组相比MDA水平降低,SOD、CAT水平升高(P<0.01),姜黄素预处理组组间差异有统计学意义(P<0.05)。(4)电镜下,HS组肝细胞内线粒体增生肿胀,嵴结构紊乱、破坏,部分肝细胞核结构破坏;姜黄素预处理组肝细胞内线粒体增生为主,无嵴结构破坏和胞核的改变。(5)HS组肝细胞质内Cyt-c表达(1.29±0.19)较Control组(0.24±0.02)明显增多(P<0.01)。姜黄素预处理组Cyt-c表达(50-cur、100-cur、200-cur分别为0.75±0.08、0.64±0.08、0.48±0.06)较HS组相对减低(P<0.05),姜黄素预处理组组间差异有统计学意义(P<0.05)。结论:干热环境热射病大鼠肝脏损伤明显,姜黄素预处理能减轻干热环境热射病导致的肝损伤,其机制可能与保护线粒体和抗氧化应激有关。姜黄素对热射病大鼠肝脏的保护作用具有剂量依赖性。 Objective: To study the protective effect and mechanism of curcumin preconditioning on the liver of dry-hot environment rats. Methods: Fifty SD rats were randomly divided into 5 groups (n = 10): normal control group, HS group, 50-cur group, 100-cur group and 200-cur group. The rats in Control group and HS group were given gavage with saline, and 50 mg / kg, 100 mg / kg and 200 mg / kg curcumin were given to the 50-cur group, 100-cur group and 200-cur group respectively Times, for 7 consecutive days. On the 8th day except for the Control group, the other 4 groups of rats were transferred to the artificial environment laboratory of Northwest China (ambient temperature 41 ± 0.5 ℃, humidity 10 ± 1%) for experiments. The first 150 minutes of the experiment, testing rectal temperature, anesthesia drawn. At the same time, the control group directly detected rectal temperature and anesthetized. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and cytochrome C ) Of the expression. Electron microscopy changes of liver cell ultrastructure. Results: (1) At the 150th minute, the body temperature of each group of rats exceeded 42 ℃, reaching the state of heat-induced fever. Curcumin pretreatment group body temperature decreased compared with HS group (P <0.01). Curcumin pretreatment group differences were not statistically significant (P> 0.05). (2) The levels of ALT and AST in HS group were higher than those in Control group (P <0.01). The levels of ALT and AST in curcumin pretreatment group were significantly lower than those in HS group (P <0.05), but curcumin pretreatment group was significantly different (P <0.05). (3) Compared with Control group, HS group had higher MDA level and lower SOD and CAT levels (P <0.01). Curcumin pretreatment group compared with the HS group MDA level decreased, SOD, CAT levels increased (P <0.01), curcumin pretreatment group difference was statistically significant (P <0.05). (4) Under electron microscope, mitochondria were proliferated, the structures of cristae were disorganized, the structures of cristae were destroyed, and the nuclear structure of some hepatocytes were destroyed. In curcumin pretreatment group, mitochondrial hyperplasia of hepatocytes was dominant, and no changes of crest structure and nucleus were observed. (5) The expression of Cyt-c in liver cytoplasm of HS group was significantly higher than that of Control group (1.29 ± 0.19) (0.24 ± 0.02) (P <0.01). Curcumin pretreatment group Cyt-c expression (50-cur, 100-cur, 200-cur were 0.75 ± 0.08,0.64 ± 0.08,0.48 ± 0.06) compared with the HS group was significantly lower (P <0.05), curcumin pretreatment The difference between the groups was statistically significant (P <0.05). CONCLUSIONS: The liver injury in rats with hot and dry heat environment is obvious. Curcumin preconditioning can reduce the liver damage caused by hot and dry environment, which may be related to the protection of mitochondria and anti-oxidative stress. Curcumin has a dose-dependent protective effect on the heat-induced rat liver.
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