益肾化浊方对SAMP8小鼠海马β淀粉样蛋白和磷酸化tau蛋白表达及肝肾功能的影响
|
摘要
目的观察益肾化浊方对快速老化小鼠SAMP8海马β淀粉样蛋白(Aβ)和磷酸化tau(p-tau)蛋白表达及肝肾功能的影响。方法将7月龄SAMP8随机分成SAMP8组、益肾化浊方(YSHZ)组,选择抗快速老化小鼠SAMR1作为对照;益肾化浊方按照6. 24 g/kg灌胃干预,SAMR1组和SAMP8组给予等体积的蒸馏水,每日灌胃1次,持续4 w;治疗后采用免疫组化法检测海马CA1区Aβ和p-tau蛋白表达,酶联免疫吸附试验(ELISA)检测血清天门冬氨酸氨基转移酶(AST)、谷丙转氨酶(ALT)水平、肌氨酸氧化酶法检测血清肌酐(Cr)水平、二乙酰-肟法检测血清尿素氮(BUN)水平。结果与SAMR1组比较,SAMP8、YSHZ组Aβ、p-tau表达量、ALT水平显著升高(P<0. 05),AST水平显著降低(P<0. 05),Cr、BUN水平无显著变化(P>0. 05);与SAMP8组比较,YSHZ组Aβ、p-tau表达量显著降低(P<0. 05),ALT、AST、Cr、BUN水平无显著变化(P>0. 05)。结论YSHZ可降低7月龄SAMP8海马CA1区Aβ和p-tau的表达,从而减轻两者的神经毒性作用,对肝肾功能未出现明显的损伤作用。
Objective To observe the effects of Yishen huazhuo prescription on β-amyloid( Aβ) and phosphorylated tau( ptau) in hippocampus and liver and renal function of SAMP8 mice. Methods 7 months old SAMP8 mice were randomly divided into SAMP8 and Yishen Huazhuo prescription groups,while senescence-resistant series 1( SAMR1) were selected as control group. Mice in Yishen Huazhuo prescription group were respectively administered the drugs according to 6. 24 g/kg and the mice in SAMR1 and SAMP8 groups were given an equal volume of distilled water. All of the mice in each group were administered once a day for 4 weeks.After finishing administration,the expressions of Aβ and p-tau protein in hippocampal CA1 region were detected by immunohistochemistry. The levels of aspartate aminotransferase( AST) and alanine aminotransferase( ALT) in serum were detected by ELISA. The levels of urea nitrogen( BUN) and creatinine( Cr) in serum were respectively detected by Sarcosine oxidase method and diacetyl hydrazine method. Results Compared with SAMR1 group,the expressions of Aβ and p-tau,the ALT levels were significantly increased in SAMP8 and YSHZ groups( P<0.05),while AST levels were significantly decreased( P<0.05) and the levels of Cr and BUN were not significantly changed( P>0.05). Compared with SAMP8 group,the expression of Aβ and p-tau in YSHZ group was significantly decreased( P<0.05); the levels of ALT,AST,Cr and BUN were not significantly changed( P>0.05). Conclusions Yishen Huazhuo prescription could reduce the expression of Aβ and p-tau in hippocampal CA1 region of 7 months old SAMP8 mice,thus alleviating the neurotoxicity of Aβ and p-tau and has no obvious injury to liver and renal function of SAMP8 mice.
Objective To observe the effects of Yishen huazhuo prescription on β-amyloid( Aβ) and phosphorylated tau( ptau) in hippocampus and liver and renal function of SAMP8 mice. Methods 7 months old SAMP8 mice were randomly divided into SAMP8 and Yishen Huazhuo prescription groups,while senescence-resistant series 1( SAMR1) were selected as control group. Mice in Yishen Huazhuo prescription group were respectively administered the drugs according to 6. 24 g/kg and the mice in SAMR1 and SAMP8 groups were given an equal volume of distilled water. All of the mice in each group were administered once a day for 4 weeks.After finishing administration,the expressions of Aβ and p-tau protein in hippocampal CA1 region were detected by immunohistochemistry. The levels of aspartate aminotransferase( AST) and alanine aminotransferase( ALT) in serum were detected by ELISA. The levels of urea nitrogen( BUN) and creatinine( Cr) in serum were respectively detected by Sarcosine oxidase method and diacetyl hydrazine method. Results Compared with SAMR1 group,the expressions of Aβ and p-tau,the ALT levels were significantly increased in SAMP8 and YSHZ groups( P<0.05),while AST levels were significantly decreased( P<0.05) and the levels of Cr and BUN were not significantly changed( P>0.05). Compared with SAMP8 group,the expression of Aβ and p-tau in YSHZ group was significantly decreased( P<0.05); the levels of ALT,AST,Cr and BUN were not significantly changed( P>0.05). Conclusions Yishen Huazhuo prescription could reduce the expression of Aβ and p-tau in hippocampal CA1 region of 7 months old SAMP8 mice,thus alleviating the neurotoxicity of Aβ and p-tau and has no obvious injury to liver and renal function of SAMP8 mice.
引文
1 Querfurth HW,Laferla FM.Alzheimer's disease[J].New Engl J Med,2010;362(4):329-44.
2 Ittner LM,G9tz J.Amyloid-βand tau--a toxic pas de deux in Alzheimer's disease[J].Nature Rev Neurosci,2011;12(2):65-72.
3 Hollister R,West H,Mui S,et al.Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease[J].Ann Neurol,1997;41(1):17-24.
4 Serranopozo A,Frosch MP,Masliah E,et al.Neuropathological alterations in Alzheimer disease[J].Cold Spring Harbor Perspect Med,2011;1(1):a006189.
5 Zhang Y,Lin C,Zhang L,et al.Cognitive improvement during treatment for mild Alzheimer's disease with a Chinese herbal formula:a randomized controlled trial[J].PLoS One,2015;10(6):e0130353.
6王雪岩,周震,张琳琳,等.淫羊藿苷对SAMP8小鼠记忆能力、神经元微观形态及GSK-3β蛋白表达的影响[J].辽宁中医杂志,2014;41(12):2707-10.
7宋宛珊,张玉莲,周震,等.益肾化浊方对快速老化小鼠认知功能与海马神经元形态学的影响及机制[J].中国老年学杂志,2016;36(11):2586-90.
8魏伟等.药理实验方法学[M].北京:人民卫生出版社,2010:45.
9张玉莲,张连城,李强,等.660例老年性痴呆患者中医证候学研究[J].中医杂志,2015;56(3):235-9.
10郑桃林,王哲,刘超,等.淫羊藿苷对阿尔茨海默病细胞模型糖原合成酶激酶-3β表达的影响及机制[J].中国老年学杂志,2016;36(4):800-2.
11 Wang K,Sun W,Zhang L,et al.Oleanolic acid ameliorates Aβ25-35injection-induced spatial learning and memory deficit in Alzheimer's disease model rats[J].CNS Neurol Disord Drug Targets,2018;17(5):389-99.
12韩文文,张玉莲,周震,等.二苯乙烯苷对Aβ25-35致神经干细胞损伤的保护作用[J].中国实验方剂学杂志,2013;19(11):160-3.
13罗兰,阿尔孜古丽·吐尔逊,王晓雯.肉苁蓉总苷对β淀粉样蛋白25-35诱导PC12细胞凋亡的保护作用[J].中国新药与临床杂志,2010;29(2):115-8.
14邓敏贞,黄丽平,方永奇.石菖蒲挥发油联合人参总皂苷对D-半乳糖联合氯化铝致阿尔茨海默病模型小鼠学习记忆能力及脑组织细胞凋亡的影响[J].中药材,2015;38(5):1018-23.
15尹淑杰,张涛,荣光影,等.川芎嗪对阿尔茨海默病大鼠学习记忆能力和细胞周期蛋白E、P21表达的影响[J].中国老年学杂志,2016;36(20):4961-2.
16 Tiraboschi P,Hansen LA,Thal LJ,et al.The importance of neuritic plaques and tangles to the development and evolution of AD[J].Neurology,2004;62(11):1984-9.
17 Theofilas P,Ehrenberg AJ,Nguy A,et al.Probing the correlation of neuronal loss,neurofibrillary tangles,and cell death markers across the Alzheimer's disease Braak stages:a quantitative study in humans[J].Neurobiol Aging,2018;61:1-12.
18 Campion D,Pottier C,Nicolas G,et al.Alzheimer disease:modeling an Aβ-centered biological network[J].Molec Psychiatry,2016;21(7):1-11.
19 Zhou L,Mcinnes J,Wierda K,et al.Tau association with synaptic vesicles causes presynaptic dysfunction[J].Nature Comm,2017;8(15295):1-13.
20 Ittner LM,Ke YD,Delerue F,et al.Dendritic function of tau mediates amyloid-βtoxicity in Alzheimer's disease mouse models[J].Cell,2010;142(3):387-97.
21 Bejanin A,Schonhaut DR,La RJ,et al.Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease[J].Brain,2017;140(12):1-15.
22徐家淳,王凯,覃启京,等.益肾化浊方对阿尔茨海默病大鼠Bcl-2/Bax及α分泌酶蛋白可溶性淀粉酶前体蛋白α表达的影响[J].中国老年学杂志,2016;36(23):5769-71.
23赵新妹,李晓宇,孙蓉,等.何首乌不同炮制品醇提物对小鼠急性毒性实验比较研究[J].中国药物警戒,2017;14(10):599-602.
24 Chen YH,Wang MF,Liao JW,et al.Beneficial effects of nicotinamide on alcohol-induced liver injury in senescence-accelerated mice[J].Biofactors,2010;34(2):97-107.
25柳颖,林慧铭.ALT、AST、GGT检测在肝脏疾病诊断中的临床价值[J].国际检验医学杂志,2015;36(17):2562-3.
2 Ittner LM,G9tz J.Amyloid-βand tau--a toxic pas de deux in Alzheimer's disease[J].Nature Rev Neurosci,2011;12(2):65-72.
3 Hollister R,West H,Mui S,et al.Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease[J].Ann Neurol,1997;41(1):17-24.
4 Serranopozo A,Frosch MP,Masliah E,et al.Neuropathological alterations in Alzheimer disease[J].Cold Spring Harbor Perspect Med,2011;1(1):a006189.
5 Zhang Y,Lin C,Zhang L,et al.Cognitive improvement during treatment for mild Alzheimer's disease with a Chinese herbal formula:a randomized controlled trial[J].PLoS One,2015;10(6):e0130353.
6王雪岩,周震,张琳琳,等.淫羊藿苷对SAMP8小鼠记忆能力、神经元微观形态及GSK-3β蛋白表达的影响[J].辽宁中医杂志,2014;41(12):2707-10.
7宋宛珊,张玉莲,周震,等.益肾化浊方对快速老化小鼠认知功能与海马神经元形态学的影响及机制[J].中国老年学杂志,2016;36(11):2586-90.
8魏伟等.药理实验方法学[M].北京:人民卫生出版社,2010:45.
9张玉莲,张连城,李强,等.660例老年性痴呆患者中医证候学研究[J].中医杂志,2015;56(3):235-9.
10郑桃林,王哲,刘超,等.淫羊藿苷对阿尔茨海默病细胞模型糖原合成酶激酶-3β表达的影响及机制[J].中国老年学杂志,2016;36(4):800-2.
11 Wang K,Sun W,Zhang L,et al.Oleanolic acid ameliorates Aβ25-35injection-induced spatial learning and memory deficit in Alzheimer's disease model rats[J].CNS Neurol Disord Drug Targets,2018;17(5):389-99.
12韩文文,张玉莲,周震,等.二苯乙烯苷对Aβ25-35致神经干细胞损伤的保护作用[J].中国实验方剂学杂志,2013;19(11):160-3.
13罗兰,阿尔孜古丽·吐尔逊,王晓雯.肉苁蓉总苷对β淀粉样蛋白25-35诱导PC12细胞凋亡的保护作用[J].中国新药与临床杂志,2010;29(2):115-8.
14邓敏贞,黄丽平,方永奇.石菖蒲挥发油联合人参总皂苷对D-半乳糖联合氯化铝致阿尔茨海默病模型小鼠学习记忆能力及脑组织细胞凋亡的影响[J].中药材,2015;38(5):1018-23.
15尹淑杰,张涛,荣光影,等.川芎嗪对阿尔茨海默病大鼠学习记忆能力和细胞周期蛋白E、P21表达的影响[J].中国老年学杂志,2016;36(20):4961-2.
16 Tiraboschi P,Hansen LA,Thal LJ,et al.The importance of neuritic plaques and tangles to the development and evolution of AD[J].Neurology,2004;62(11):1984-9.
17 Theofilas P,Ehrenberg AJ,Nguy A,et al.Probing the correlation of neuronal loss,neurofibrillary tangles,and cell death markers across the Alzheimer's disease Braak stages:a quantitative study in humans[J].Neurobiol Aging,2018;61:1-12.
18 Campion D,Pottier C,Nicolas G,et al.Alzheimer disease:modeling an Aβ-centered biological network[J].Molec Psychiatry,2016;21(7):1-11.
19 Zhou L,Mcinnes J,Wierda K,et al.Tau association with synaptic vesicles causes presynaptic dysfunction[J].Nature Comm,2017;8(15295):1-13.
20 Ittner LM,Ke YD,Delerue F,et al.Dendritic function of tau mediates amyloid-βtoxicity in Alzheimer's disease mouse models[J].Cell,2010;142(3):387-97.
21 Bejanin A,Schonhaut DR,La RJ,et al.Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease[J].Brain,2017;140(12):1-15.
22徐家淳,王凯,覃启京,等.益肾化浊方对阿尔茨海默病大鼠Bcl-2/Bax及α分泌酶蛋白可溶性淀粉酶前体蛋白α表达的影响[J].中国老年学杂志,2016;36(23):5769-71.
23赵新妹,李晓宇,孙蓉,等.何首乌不同炮制品醇提物对小鼠急性毒性实验比较研究[J].中国药物警戒,2017;14(10):599-602.
24 Chen YH,Wang MF,Liao JW,et al.Beneficial effects of nicotinamide on alcohol-induced liver injury in senescence-accelerated mice[J].Biofactors,2010;34(2):97-107.
25柳颖,林慧铭.ALT、AST、GGT检测在肝脏疾病诊断中的临床价值[J].国际检验医学杂志,2015;36(17):2562-3.