首页|柴胡加龙骨牡蛎汤对肝郁大鼠肝脏脂质代谢及SREBP-1c/FAS信号通路的影响

柴胡加龙骨牡蛎汤对肝郁大鼠肝脏脂质代谢及SREBP-1c/FAS信号通路的影响

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目的 探讨柴胡加龙骨牡蛎汤对肝郁大鼠肝脏脂质代谢及固醇调节元件结合蛋白-1c/脂肪酸合酶(SREBP-1c/FAS)信号通路的影响。方法 将50 只雄性SPF级SD大鼠随机分为空白组、模型组、氟西汀组、柴胡加龙骨牡蛎低剂量组、柴胡加龙骨牡蛎高剂量组,每组10 只。空白组正常喂养,其余组大鼠采用慢性温和不可预知应激(CUMS)方法建立肝郁模型。建模成功后,氟西汀组每天给予盐酸氟西汀0。003 g/kg灌胃,柴胡加龙骨牡蛎低、高剂量组分别每天给予柴胡加龙骨牡蛎汤1。625 g/kg和3。25 g/kg灌胃,空白组和模型组给予等体积的生理盐水灌胃,均1 次/d,连续灌胃4 周。分别于造模前、成模后及灌胃结束后对大鼠进行称重,进行行为学实验(糖水偏嗜实验、旷场实验、悬尾实验);灌胃结束后处死大鼠,HE染色、油红O染色观察肝脏病理变化,取血检测血脂指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]水平,采用Western blot 法检测肝脏组织中SREBP-1c和FAS蛋白表达情况,采用RT-PCR法检测肝脏组织中SREBP-1c和FAS mRNA表达情况。结果 与空白组比较,灌胃结束后模型组大鼠体重、糖水偏嗜率、水平运动得分、垂直运动得分均明显降低(P均<0。05),悬尾不动时间均明显延长(P<0。05),出现肝脏增大、脂滴空泡化及肝细胞脂肪堆积,血清TG、TC、LDL-C水平均明显升高(P 均<0。05),血清 HDL-C 水平明显降低(P<0。05),肝脏组织中SREBP-1c和FAS蛋白及mRNA相对表达量均明显升高(P均<0。05)。与模型组比较,各给药组大鼠体重、糖水偏嗜率、水平运动得分、垂直运动得分均明显增加(P均<0。05),悬尾不动时间均明显缩短(P均<0。05),肝脏病理改变明显减轻,血清TG、TC、LDL-C水平均明显降低(P均<0。05),血清HDL-C水平均明显升高(P均<0。05),肝脏组织中SREBP-1c和FAS蛋白及mRNA相对表达量均明显降低(P均<0。05)。结论 柴胡加龙骨牡蛎汤对肝郁大鼠的肝脏脂质代谢有调节作用,机制可能与调控SREBP-1c/FAS信号通路相关。
Effects of Bupleurum plus Dragon's Bone and Oyster Decoction on hepatic lipid metabolism and SREBP-1c/FAS signaling pathway in rats with liver depression syndrome
Objective It is to investigate the effects of Bupleurum plus Dragon's Bone and Oyster Decoction(BD-BOD)on hepatic lipid metabolism and sterol regulatory element binding protein-1c/fatty acid synthase(SREBP-1c/FAS)signaling pathway in rats with liver depression syndrome.Methods Fifty male SPF-grade SD rats were randomly divided in-to blank group,model group,fluoxetine group,BDBOD low-dose group and BDBOD high-dose group,with 10 rats in each group.The blank group was fed normally,and the rats in the other groups were given chronic unpredictable mild stress(CUMS)to establish models of liver depression syndrome.After successful modeling,the fluoxetine group was given fluoxe-tine hydrochloride 0.003 g/kg by gavage,the low and high dose groups of BDBOD were given BDBOD 1.625 g/kg and 3.25 g/kg by gavage,respectively,and the blank group and model group were given equal volumes of normal saline by ga-vage,all once daily,continuously treated for 4 weeks.The rats were weighed before modeling,after modeling and at the end of gavage,and were tested by behavioral experiments(sugar-water bias test,open field test,tail suspension test);these rats were executed at the end of gavage,and pathological changes of liver were observed by HE staining and oil red O staining,their blood was taken to determine the levels of lipid indices[total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and the expressions of SREBP-1c and FAS protein in liver tissues were detected by Western blot method,the expressions of SREBP-1c and FAS mRNA in liver tissues were detected by RT-PCR.Results Compared with the blank group,the body weight,sugar-water bias rate,horizontal movement score,vertical movement score of the rats in the model group were significantly decreased at the end of gavage(all P<0.05),the tail suspension immobility time was significantly increased(P<0.05),with liver enlarge-ment,vacuolization of lipid droplets and hepatocyte fat accumulation,the serum levels of TG,TC,LDL-C were significant-ly increased(all P<0.05),the serum level of HDL-C was significantly reduced(P<0.05),and the relative expressions of SREBP-1c and FAS protein and mRNA in liver tissues were significantly increased(all P<0.05).Compared with the model group,the body weight,sugar-water bias rate,horizontal movement score and vertical movement score of the rats in each treatment group were significantly increased(all P<0.05),the tail suspension immobilization times were significant-ly shortened(all P<0.05),the pathological changes of the liver were significantly improved,the levels of serum TG,TC,and LDL-C were all significantly decreased(all P<0.05),the levels of serum HDL-C were all significantly increased(all P<0.05),and the relative expressions of SREBP-1c and FAS proteins and mRNA in liver tissues were significantly re-duced(all P<0.05).Conclusion Bupleurum plus Dragon's Bone and Oyster Decoction can regulate hepatic lipid metab-olism in rats with liver depression syndrome,and the mechanism may be related to the regulation of SREBP-1c/FAS signa-ling pathway.

liver depressionBupleurum plus Dragon's Bone and Oyster Decoctionlipid metabolismsterol regula-tory element binding protein-1cfatty acid synthase

洪捷、蔡萧君

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黑龙江省中医药科学院,黑龙江 哈尔滨 150000

肝郁 柴胡加龙骨牡蛎汤 脂质代谢 固醇调节元件结合蛋白-1c 脂肪酸合酶

黑龙江省中医药科研项目

ZHY2020-054

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(1)
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