机构地区:[1]河南中医学院药学院,郑州450046 [2]呼吸疾病诊疗与新药研发河南省协同创新中心,郑州450046 [3]黑龙江中医药大学药学院,哈尔滨150040
出 处:《世界科学技术-中医药现代化》2015年第3期464-470,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基 金:科学技术部国家重点基础研究发展计划"973计划"项目(2013CB531802):宣泻利水中药的药性研究;负责人:郑晓珂
摘 要:目的:研究桑白皮化学拆分组分对糖尿病小鼠模型物质代谢及能量代谢的影响,以期阐释中药性(气)味科学内涵的新假说。方法:雄性昆明种小鼠,腹腔注射大剂量链脲佐菌素(STZ)(170 mg·kg-1),建立Ⅰ型糖尿病小鼠模型,连续给药4周,采用酶联免疫分析(ELISA)检测葡萄糖激酶(GCK)、糖原磷酸化酶(PYGL)、丙酮酸脱氢酶(PDH)、α-酮戊二酸脱氢酶(α-KGDHC)、磷酸甘油酸激酶(PGK)、乙酰辅酶A(acetyl-Co A)、腺苷酸激酶(ADK)、延胡索酸酶(FUM)、细胞色素C还原酶(CCR)、细胞色素C氧化酶(COX)等指标,采用酶法检测ATP合酶(ATPs)、NAD与NADH含量及比值、心肌细胞Na+-K+ATP酶及ATP和ADP含量等。结果:模型组小鼠PYGL表达升高,GCK和PDH表达降低,提示葡萄糖来源增加而去路减少,体内血糖水平升高;COX表达降低,呼吸链受阻,反馈调节氧化磷酸化及底物水平磷酸化等过程,使CCR、ATPs、NAD+、PGK、α-KGDHC、ADK表达上调,而FUM表达下调,Na+-K+ATP酶活性显著降低,出现代谢紊乱;桑白皮水煎液及拆分组分能显著升高糖尿病小鼠物质代谢中GCK及PDH水平,降低糖尿病小鼠PYGL、α-KGDHC、PGK和acetyl-Co A的水平(P<0.05或P<0.01);同时升高糖尿病小鼠能量代谢中ATP、FUM、心肌细胞Na+-K+ATP酶、COX的水平(P<0.05),降低糖尿病小鼠NAD+、CCR、ATPs的水平(P<0.05或P<0.01)。结论:桑白皮水煎液及拆分组分可以有效改善糖尿病小鼠物质代谢及能量代谢紊乱,其改善作用可能与桑白皮寒凉药性密切相关。This article was aimed to study the impact on substance and energy metabolism by chemical split fractions of Mori Cortex among hypoglycemic diabetic mouse model, in order to explain the new hypothesis of the science connotation in nature and flavor of traditional Chinese medicine (TCM). Male Kunming mice were intraperitoneally injected with a large dose of streptozotocin (STZ) (170 mg'kg〈) to establish type 1 diabetes mellitus mouse model. Medication was given consecutively for four weeks. The enzyme-linked immunesorbent assay (ELISA) was used to detect glucosekinase (GCK), glycogen phosphorylase (PYGL), pyruvate dehydrogenase (PDH), a-ketoglutarate dehydrogenase (a-KGDHC), phosphoglycerate kinase (PGK), aeetyl coenzyme A (acetyl-CoA), adenylate kinase (ADK), fumarase (FUM), cytochrome C reductase (CCR), cytochrome C oxidase (COX) and other indicators. Enzymatic detection was used to determine the content of ATP coenzyme (ATPs), the content and ratio of NAD and NADH, the content of myocardial cell Na+-K~ ATP enzyme, as well as the content of ATP and ADP. The results showed that in the model group, the expression of PYGL was increased; and the expressions of GCK and PDH were decreased. It prompted that the source of glucose increased and the expelling of glucose decreased. The glucose level was increased. The COX expression was reduced and the respiratory chain was blocked. It regulated oxidative phosphorylation and the substrate phosphorylation level. It upregulated the expression of CCR, ATPs, NAD+, PGK, a-KGDHC and ADK. However, the expression of FUM was decreased. The activity of Na+-K+ ATPase was decreased significantly. At last, the metabolic disorders appeared. Mori Cortex aqueous extracts and the chemical split fractions significantly increased the GCK and PDH level in substance metabolism among diabetic mice. The levels of PYGL, a-KGDHC, PGK and acetyl-CoA were decreased (P 〈 0.05, or P 〈0.01). Meanwhile, it increased ATP and
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