鹰嘴豆总皂苷的调脂降糖作用及机制研究
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摘要
目的：
考察药食植物鹰嘴豆提取物、鹰嘴豆总皂苷(TSCAⅠ和TSCAⅡ)对采用实验法制备2型糖尿病(T2DM)大鼠体内血脂和血糖的影响,从血脂、糖代谢、组织病理变化、抗氧化及基因水平等方面探讨其抗2型糖尿病的可能作用机制和靶点。
方法：
通过连续给予SD大鼠4w高脂饲料合并联合注射浓度为45mg·Kg-1的链脲佐菌素(STZ)溶液复制2型糖尿病大鼠动物模型。
模型复制后,设正常对照组、模型组、阳性药1二甲双胍组(0.25g·Kg-1)、阳性药2血脂康组(0.14g.Kg-1)、鹰嘴豆提取物A配方低(0.7g·Kg-1)、中(1.4g·Kg-1)、高(2.8g·Kg-1)三个剂量组以及鹰嘴豆提取物B配方低(0.8g·Kg-1)、中(1.6g·Kg-1)、高(3.2g·Kg-1)三个剂量组,灌胃给药,每日1次,连续给药4w后,观察大鼠体重变化、肝脏指数、空腹血糖(FPG)水平、血清胰岛素(FIns)水平、血清胆固醇(TC)水平、甘油三酯(TG)水平、高密度脂蛋白(HDL-C)水平、低密度脂蛋白(LDL-C)水平的改变,并通过公式计算得到肝脏指数、胰岛素敏感指数(ISI),同时观测各组大鼠肝脏、肾脏的组织病理学变化情况。
鹰嘴豆提取物经分离纯化后,得到鹰嘴豆总皂苷(TSCA Ⅰ和TSCAⅡ)。采用建立的2型糖尿病脂代谢紊乱大鼠模型,设正常对照组、模型组、二甲双胍组(0.1g.Kg-1)、TSCAⅠ低(0.1g·Kg-1)、高(0.3g·Kg-1)两个剂量组和和TSCAⅡ低(0.1g·Kg-1)、高(0.3g·Kg-1)两个剂量组,灌胃给药,每日1次,连续给药4w后,观察大鼠体重变化,通过检测大鼠FPG和FIns水平,以及TC、TG、HDL-C和LDL-C水平的变化,通过公式计算得到胰岛素抵抗指数(IRI)改变,测定血清游离脂肪酸(FFA)、白介素-6(IL-6)、肌/肝糖原(MG/HG)、骨骼肌中己糖激酶(HK)活性的变化,同时观察胰腺的病理改变；测定血清中肌酐(Scr)、尿素氮(BUN)、血管紧张素Ⅱ(ATⅡ)、内皮素-1(ET-1)的含量,血浆中血栓素B(TXB2)和6酮-前列腺素(6-Keto-PGF1α)的含量,考察TSCA对血管活性物质的影响；通过总过氧化物歧化酶(TSOD)、过氧化氢酶(CAT)、丙二醛(MDA)、总一氧化氮酶(TNOS)活性的检测,考察TSCA抗氧化活性；最后检测PPAR-γ基因转录水平。
结果：
与模型组相比,鹰嘴豆提取物配方A、配方B各剂量组都能够降低实验性2型糖尿病模型大鼠的肝脏指数。同时均能够降低模型大鼠血清中得血糖水平,升高胰岛素敏感指数,但各剂量组影响血清胰岛素水平较小。鹰嘴豆提取物配方A各剂量组均能降低模型大鼠胆固醇水平,低、中剂量组能降低甘油三酯和低密度脂蛋白水平。鹰嘴豆提取物配方B各剂量组均能够降低模型大鼠低密度脂蛋白的水平,低、中剂量组能降低甘油三酯、胆固醇的水平。而鹰嘴豆提取物的两个配方比较,除甘油三酯水平略有差异,二者在调节血脂降低血糖方面的作用,基本上无显著性差异。病理学检查结果,我们可以得出鹰嘴豆提取物配方A、配方B各剂量组全都能够有效地改善和治愈实验性2型糖尿病模型建立对模型大鼠肝脏、肾脏等器官所造成的损害。
鹰嘴豆总皂苷各剂量组与模型组比较,FPG、TC、TG、LDL-C、FInss、IRI、 FFA水平及IL-6含量下降,HDL-C/TC、BUN、Scr、MG和HG含量以及HK的活性升高(P<0.05,P<0.01),对2型糖尿病造模所致的胰岛损伤有一定的修复作用；且TSCA Ⅱ的降糖作用优于TSCA Ⅰ:鹰嘴豆总皂苷能够降低糖尿病大鼠,血浆中TXB2和6-Keto-PGF1α等血管活性物质,对肾血管具有一定的修复作用；抗氧化指标的结果表明TSCA能够改善2型糖尿病大鼠的抗氧化能力；此外TSCA能够升高2型糖尿病大鼠PPAR-γ基因转录水平。
结论：
鹰嘴豆提取物及总皂苷有较好的降低血糖、调节血脂的作用,其作用机制可能与改善胰岛素抵抗,同时提高外周组织利用糖的能力、修复胰岛和肾血管,增强抗氧化能力以及提高PPAR-γ基因转录水平。
Objective:
To observe the effects of Cicerarinum extract and Total Saponins of Cicer Arietinum (TSCA Ⅰ and TSCAⅡ) onglucose lipid metabolism of type2diabetes rats and to discuss the mechanism from different aspect preliminarily.
Methods:
Animal model of type2diabeteswas established by a high fat dietwith intraperitoneal injection of streptozocin (low dose) into male SD rats separated to10groups:controlgroup, modelgroup, metformingroup, Lovastatingroup low-dose (0.7g·Kg-1), middle-dose (1.4g·Kg-1), high-dose (2.8g·Kg-1) of compound A and low-dose (0.8g·Kg-1), middle-dose (1.6g·Kg-1), high-dose (3.2g·Kg-1) of compound B of Cicerari-numl extract. After4weeks treatment (once a day), weigh them. The level of fasting plasmaglucose (FPG), fasting insulin (FIns), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulin sensitivity index (ISI) and the pathological changes of the liver and kidneywere evaluated.
Animal model of type2diabeteswas established andgive controlgroup, modelgroup, metformingroup (0.1g·Kg-1), low-dose (0.1g·Kg-1), high-dose (0.3g·Kg-1) of Cicer Arietinum Total Saponins (TSCA Ⅰ and TSCA Ⅱ). After4weeks treatment (one time a day), weight them. The level of FPG, FIns, TC, TG, HDL-C, LDL-C, insulin resistance index (IRI), free fatty acid (FFA), interleukin (IL-6), muscleglycogen/hepaticglycogen (MG/HG), hexokinase (HK) in muscle and the pathological changes of the liver and kidneywere evaluated ISI and the pathological changes of the pancreaswere evaluated. Serum creatinine (Scr), blood urea nitrogen (BUN), angiotensin Ⅱ(AT Ⅱ), endothelin-1 (ET-1) content, plasma thromboxane B (TXB2) and6-Keto-PGF1α in the content, to examine the impact of TSCA substances of the blood vessels; total superoxide dismutase (TSOD), catalase (CAT), malondialdehyde (MDA), total nitric oxide enzyme (TNOS) activity detection, inspection TSCA antioxidant activity; detect the level of PPAR-ygene transcription.
Results:
Comparedwith modelgroup, the liver index in Cicerarinuml extractgroup declined, the level of FPG declined and ISI increased-except low-dosegroup of compound B, the level of TC of high-dosegroup of compound A declined, the level of LDL-C of high-dosegroup of compound B declined, and the levels of TG, TC, LDL-C of all others Cicerarinuml extractgroup declined. Cicerarinuml extractgroup can lighten the pathological lesion of the liver and kidney.
Comparedwith the modelgroup, the level of FPG, TC, TG, LDL-C, FIns, IRI, FFA of blood serum and IL-6were reduced significantly by treatedwith TSCA Ⅰ and TSCAⅡ (P <0.05, P<0.01), however the HDL-C/TC, MG, HG and the activity of hexokinasewere elevatated significantly (P<0.05, P<0.01), injured pancreatic isletwere regulated aswell. And the TSCA Ⅱ had better effect than TSCA Ⅰ in decreasing hyperglycemia. TSCA Ⅱ to reduce diabetic rats TXB2and6-Keto-PGF1α in and other vascular substances, renal vascular repair; the TSCAⅡ can improve the antioxidant capacity of type2diabetic rats, and its main active site is the liver, kidney andskeletal muscle; followed by TSCAⅡ increase in type2diabetic rats PPAR-ygene transcription level.
Conclusions:
Cicerarinuml extract and TSCA can adjust the bloodglucose and lipid effectively. The possible mechanism is considered to reduce the level of FFA and IL-6in order to ameliorate IR and elevatate the activity of hexokinase andglycogen, Repair of pancreatic islets and renal blood vessels, increase the antioxidant capacity and increase PPAR-ygene transcription level.
考察药食植物鹰嘴豆提取物、鹰嘴豆总皂苷(TSCAⅠ和TSCAⅡ)对采用实验法制备2型糖尿病(T2DM)大鼠体内血脂和血糖的影响,从血脂、糖代谢、组织病理变化、抗氧化及基因水平等方面探讨其抗2型糖尿病的可能作用机制和靶点。
方法：
通过连续给予SD大鼠4w高脂饲料合并联合注射浓度为45mg·Kg-1的链脲佐菌素(STZ)溶液复制2型糖尿病大鼠动物模型。
模型复制后,设正常对照组、模型组、阳性药1二甲双胍组(0.25g·Kg-1)、阳性药2血脂康组(0.14g.Kg-1)、鹰嘴豆提取物A配方低(0.7g·Kg-1)、中(1.4g·Kg-1)、高(2.8g·Kg-1)三个剂量组以及鹰嘴豆提取物B配方低(0.8g·Kg-1)、中(1.6g·Kg-1)、高(3.2g·Kg-1)三个剂量组,灌胃给药,每日1次,连续给药4w后,观察大鼠体重变化、肝脏指数、空腹血糖(FPG)水平、血清胰岛素(FIns)水平、血清胆固醇(TC)水平、甘油三酯(TG)水平、高密度脂蛋白(HDL-C)水平、低密度脂蛋白(LDL-C)水平的改变,并通过公式计算得到肝脏指数、胰岛素敏感指数(ISI),同时观测各组大鼠肝脏、肾脏的组织病理学变化情况。
鹰嘴豆提取物经分离纯化后,得到鹰嘴豆总皂苷(TSCA Ⅰ和TSCAⅡ)。采用建立的2型糖尿病脂代谢紊乱大鼠模型,设正常对照组、模型组、二甲双胍组(0.1g.Kg-1)、TSCAⅠ低(0.1g·Kg-1)、高(0.3g·Kg-1)两个剂量组和和TSCAⅡ低(0.1g·Kg-1)、高(0.3g·Kg-1)两个剂量组,灌胃给药,每日1次,连续给药4w后,观察大鼠体重变化,通过检测大鼠FPG和FIns水平,以及TC、TG、HDL-C和LDL-C水平的变化,通过公式计算得到胰岛素抵抗指数(IRI)改变,测定血清游离脂肪酸(FFA)、白介素-6(IL-6)、肌/肝糖原(MG/HG)、骨骼肌中己糖激酶(HK)活性的变化,同时观察胰腺的病理改变；测定血清中肌酐(Scr)、尿素氮(BUN)、血管紧张素Ⅱ(ATⅡ)、内皮素-1(ET-1)的含量,血浆中血栓素B(TXB2)和6酮-前列腺素(6-Keto-PGF1α)的含量,考察TSCA对血管活性物质的影响；通过总过氧化物歧化酶(TSOD)、过氧化氢酶(CAT)、丙二醛(MDA)、总一氧化氮酶(TNOS)活性的检测,考察TSCA抗氧化活性；最后检测PPAR-γ基因转录水平。
结果：
与模型组相比,鹰嘴豆提取物配方A、配方B各剂量组都能够降低实验性2型糖尿病模型大鼠的肝脏指数。同时均能够降低模型大鼠血清中得血糖水平,升高胰岛素敏感指数,但各剂量组影响血清胰岛素水平较小。鹰嘴豆提取物配方A各剂量组均能降低模型大鼠胆固醇水平,低、中剂量组能降低甘油三酯和低密度脂蛋白水平。鹰嘴豆提取物配方B各剂量组均能够降低模型大鼠低密度脂蛋白的水平,低、中剂量组能降低甘油三酯、胆固醇的水平。而鹰嘴豆提取物的两个配方比较,除甘油三酯水平略有差异,二者在调节血脂降低血糖方面的作用,基本上无显著性差异。病理学检查结果,我们可以得出鹰嘴豆提取物配方A、配方B各剂量组全都能够有效地改善和治愈实验性2型糖尿病模型建立对模型大鼠肝脏、肾脏等器官所造成的损害。
鹰嘴豆总皂苷各剂量组与模型组比较,FPG、TC、TG、LDL-C、FInss、IRI、 FFA水平及IL-6含量下降,HDL-C/TC、BUN、Scr、MG和HG含量以及HK的活性升高(P<0.05,P<0.01),对2型糖尿病造模所致的胰岛损伤有一定的修复作用；且TSCA Ⅱ的降糖作用优于TSCA Ⅰ:鹰嘴豆总皂苷能够降低糖尿病大鼠,血浆中TXB2和6-Keto-PGF1α等血管活性物质,对肾血管具有一定的修复作用；抗氧化指标的结果表明TSCA能够改善2型糖尿病大鼠的抗氧化能力；此外TSCA能够升高2型糖尿病大鼠PPAR-γ基因转录水平。
结论：
鹰嘴豆提取物及总皂苷有较好的降低血糖、调节血脂的作用,其作用机制可能与改善胰岛素抵抗,同时提高外周组织利用糖的能力、修复胰岛和肾血管,增强抗氧化能力以及提高PPAR-γ基因转录水平。
Objective:
To observe the effects of Cicerarinum extract and Total Saponins of Cicer Arietinum (TSCA Ⅰ and TSCAⅡ) onglucose lipid metabolism of type2diabetes rats and to discuss the mechanism from different aspect preliminarily.
Methods:
Animal model of type2diabeteswas established by a high fat dietwith intraperitoneal injection of streptozocin (low dose) into male SD rats separated to10groups:controlgroup, modelgroup, metformingroup, Lovastatingroup low-dose (0.7g·Kg-1), middle-dose (1.4g·Kg-1), high-dose (2.8g·Kg-1) of compound A and low-dose (0.8g·Kg-1), middle-dose (1.6g·Kg-1), high-dose (3.2g·Kg-1) of compound B of Cicerari-numl extract. After4weeks treatment (once a day), weigh them. The level of fasting plasmaglucose (FPG), fasting insulin (FIns), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulin sensitivity index (ISI) and the pathological changes of the liver and kidneywere evaluated.
Animal model of type2diabeteswas established andgive controlgroup, modelgroup, metformingroup (0.1g·Kg-1), low-dose (0.1g·Kg-1), high-dose (0.3g·Kg-1) of Cicer Arietinum Total Saponins (TSCA Ⅰ and TSCA Ⅱ). After4weeks treatment (one time a day), weight them. The level of FPG, FIns, TC, TG, HDL-C, LDL-C, insulin resistance index (IRI), free fatty acid (FFA), interleukin (IL-6), muscleglycogen/hepaticglycogen (MG/HG), hexokinase (HK) in muscle and the pathological changes of the liver and kidneywere evaluated ISI and the pathological changes of the pancreaswere evaluated. Serum creatinine (Scr), blood urea nitrogen (BUN), angiotensin Ⅱ(AT Ⅱ), endothelin-1 (ET-1) content, plasma thromboxane B (TXB2) and6-Keto-PGF1α in the content, to examine the impact of TSCA substances of the blood vessels; total superoxide dismutase (TSOD), catalase (CAT), malondialdehyde (MDA), total nitric oxide enzyme (TNOS) activity detection, inspection TSCA antioxidant activity; detect the level of PPAR-ygene transcription.
Results:
Comparedwith modelgroup, the liver index in Cicerarinuml extractgroup declined, the level of FPG declined and ISI increased-except low-dosegroup of compound B, the level of TC of high-dosegroup of compound A declined, the level of LDL-C of high-dosegroup of compound B declined, and the levels of TG, TC, LDL-C of all others Cicerarinuml extractgroup declined. Cicerarinuml extractgroup can lighten the pathological lesion of the liver and kidney.
Comparedwith the modelgroup, the level of FPG, TC, TG, LDL-C, FIns, IRI, FFA of blood serum and IL-6were reduced significantly by treatedwith TSCA Ⅰ and TSCAⅡ (P <0.05, P<0.01), however the HDL-C/TC, MG, HG and the activity of hexokinasewere elevatated significantly (P<0.05, P<0.01), injured pancreatic isletwere regulated aswell. And the TSCA Ⅱ had better effect than TSCA Ⅰ in decreasing hyperglycemia. TSCA Ⅱ to reduce diabetic rats TXB2and6-Keto-PGF1α in and other vascular substances, renal vascular repair; the TSCAⅡ can improve the antioxidant capacity of type2diabetic rats, and its main active site is the liver, kidney andskeletal muscle; followed by TSCAⅡ increase in type2diabetic rats PPAR-ygene transcription level.
Conclusions:
Cicerarinuml extract and TSCA can adjust the bloodglucose and lipid effectively. The possible mechanism is considered to reduce the level of FFA and IL-6in order to ameliorate IR and elevatate the activity of hexokinase andglycogen, Repair of pancreatic islets and renal blood vessels, increase the antioxidant capacity and increase PPAR-ygene transcription level.
引文
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