新博柴黄颗粒对内毒素致热新西兰兔解热机制研究
发布时间：2018-08-08 12:04
【摘要】：第一部分新博柴黄颗粒对内毒素致热新西兰兔的解热作用 背景 发热是一种临床上的常见症状，是一个含有多个环节、由多个因素共同参与的复杂过程，抑制或阻断发热过程中的某些环节可产生解热效应，达到防治体温升高或降低体温的目的。 新博柴黄颗粒的主要成分为黄芩苷和柴胡苷[1]，柴胡、黄芩是古方小柴胡汤“和解少阳”的核心药对[2]。新博柴黄颗粒在临床应用广泛，解热效果显著，但是新博柴黄颗粒的解热机制尚不清楚，需进一步的研究。 目的: 研究新博柴黄颗粒对内毒素致热新西兰兔模型的解热作用。 方法: 90只新西兰兔，随机分为对照组（灌胃生理盐水10ml/kg+耳缘静脉注射生理盐水0.3ug/kg）；发热组（灌胃生理盐水10ml/kg+耳缘静脉注射内毒素0.3ug/kg）；柴黄1组（灌胃新博柴黄液10ml/kg共含柴黄8g+耳缘静脉注射内毒素0.3ug/kg）；柴黄2组（灌胃新博柴黄液10ml/kg共含柴黄4g+耳缘静脉注射内毒素0.3ug/kg）；柴黄3组（灌胃新博柴黄液10ml/kg共含柴黄2g+耳缘静脉注射内毒素0.3ug/kg）。每0.5小时测量肛温一次，共5小时。 结果: 新博柴黄颗粒不同剂量组均具有降低发热新西兰兔体温的作用，柴黄1组解热作用明显优于2或3组。 结论: 新博柴黄颗粒对内毒素致热新西兰兔有明显的解热作用。 第二部分新博柴黄颗粒对内毒素致热新西兰兔血清、脑脊液中内生致热原的影响 背景 发热是临床上多种疾病的常见症状，其机制主要为外源性致热原作用于体内单核巨噬细胞产生并释放EP,近年来发现的EP包括白介素(IL-1β)、肿瘤坏死因子-α(TNF-α)、干扰素(IFN)、巨噬细胞炎症蛋白-1(MIP-1)、IL-6等,EP将发热信息直接或间接送达下丘脑,下丘脑释放发热介质引起发热。 目的： 研究新博柴黄颗粒对内毒素致热新西兰兔模型内生致热原的影响,进一步阐明新博柴黄颗粒的解热作用机制。 方法: 90只新西兰兔，随机分为对照组（灌胃生理盐水10ml/kg+耳缘静脉注射生理盐水0.3ug/kg）；发热组（灌胃生理盐水10ml/kg+耳缘静脉注射内毒素0.3ug/kg）；柴黄1组（灌胃新博柴黄液10ml/kg共含柴黄8g+耳缘静脉注射内毒素0.3ug/kg）；柴黄2组（灌胃新博柴黄液10ml/kg共含柴黄4g+耳缘静脉注射内毒素0.3ug/kg）；柴黄3组（灌胃新博柴黄液10ml/kg共含柴黄2g+耳缘静脉注射内毒素0.3ug/kg）。每0.5小时测量肛温一次，共5小时，用放射免疫法（RIA）测定两个发热高峰血清及脑脊液中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)含量。并将柴黄3个剂量组的温度变化抑制率与IL-1β、TNF-α、IL-6含量变化抑制率分别作相关性分析。 结果: 新博柴黄颗粒不同剂量组均具有降低发热新西兰兔体温的作用，具有降低脑脊液及血清中IL-1β、TNF-α和IL-6含量作用。柴黄1组解热作用明显优于2或3组。相关分析表明，新博柴黄颗粒对新西兰兔的体温变化抑制率与致热后1h、3h新西兰兔血清、脑脊液中IL-1β、IL-6、TNF-α含量变化抑制率之间呈正相关(P0.05)。 结论: 1.新博柴黄颗粒可明显降低内毒素致热新西兰兔血液及脑脊液中的内生致热原IL-1β、TNF-α和IL-6； 2.新博柴黄颗粒的解热作用机制可能与减少血液及脑脊液中内生致热原IL-1β、TNF-α和IL-6的含量有关。 第三部分新博柴黄颗粒对内毒素致热新西兰兔脑脊液、下丘脑中中枢性发热介质的影响 背景： 发热是一个由多因子参与及相互作用的复杂过程，其机制为发热激活物作用于某些细胞产生和释放内生致热原(EP)， EP作用于下丘脑产生中枢性发热介质，中枢性发热介质再作用于体温调节中枢使调定点上移，产热增加，散热减少，体温上升，从而导致发热。抑制或阻断EP和/或中枢性发热介质可产生解热效应，达到防治体温升高或降低体温的目的。 现已知的中枢性发热介质包括促肾上腺皮质激素释放激素(CRH)、前列腺素E2(PGE2)、精氨酸加压素(AVP)和黑素细胞刺激素(α-MSH)等。 目的： 研究新博柴黄颗粒对内毒素致热新西兰兔模型脑脊液、下丘脑中中枢性发热介质的影响,进一步阐明新博柴黄颗粒的解热作用机制。 方法: 90只新西兰兔，随机分为对照组（灌胃生理盐水10ml/kg+耳缘静脉注射生理盐水0.3ug/kg）；发热组（灌胃生理盐水10ml/kg+耳缘静脉注射内毒素0.3ug/kg）；柴黄1组（灌胃新博柴黄液10ml/kg共含柴黄8g+耳缘静脉注射内毒素0.3ug/kg）；柴黄2组（灌胃新博柴黄液10ml/kg共含柴黄4g+耳缘静脉注射内毒素0.3ug/kg）；柴黄3组（灌胃新博柴黄液10ml/kg共含柴黄2g+耳缘静脉注射内毒素0.3ug/kg）。每0.5小时测量肛温一次，共5小时，用放射免疫法（RIA）测定两个发热高峰脑脊液及下丘脑组织中前列腺素E2(PGE2)、精氨酸加压素(AVP)含量。并将柴黄3个剂量组的温度变化抑制率PGE2和AVP含量变化抑制率分别作相关性分析。 结果: 新博柴黄颗粒不同剂量组均具有降低发热新西兰兔体温的作用，具有降低脑脊液和下丘脑中PGE2的作用，具有升高脑脊液和下丘脑中AVP含量的作用。柴黄1组解热作用明显优于2或3组。相关分析表明，新博柴黄颗粒对新西兰兔的体温变化抑制率与致热后1h、3h新西兰兔脑脊液、下丘脑中PGE2含量变化抑制率之间呈正相关(P0.05)，与致热后3h脑脊液、下丘脑中AVP含量变化抑制率之间呈负相关（P0.05）。 结论: 1.新博柴黄颗粒对内毒素致热新西兰兔脑脊液和下丘脑中的PGE2、AVP产生明显影响； 2.新博柴黄颗粒的解热作用机制可能与减少中枢性正调节介质PGE2，，增加中枢性负调节介质AVP有关。
[Abstract]:Part one: the antipyretic effect of Xin Bo Chai Huang Granule on endotoxin induced fever in New Zealand rabbits.
background
Fever is a common clinical symptom. It is a complex process involving multiple links and multiple factors. It can inhibit or block some parts of the fever process to produce antipyretic effect and achieve the purpose of preventing temperature rise or lowering body temperature.
The main components of Xin Bo Chai Huang granules are baicalin and [1], bupleurum and scutellaria are the core drugs of ancient Xiao Chaihu soup "reconciliation Shaoyang", which are widely used in the clinical application of [2]. Xin Bo Chai Huang granules. The Antipyretic Mechanism of Xin Bo Chai Huang granules is not clear, and it needs further study.
Objective:
To study the antipyretic effect of Xin Bo Chai Huang Granule on endotoxin induced fever in New Zealand rabbits.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid containing the injection of endotoxin 0.3ug/kg in the vein of Chai Huang 4g+ ear, and 3 groups of Chai Huang (Chai Huang Chai Huang liquid 10ml/kg, including endotoxin 0.3ug/kg injected with Chai Huang 2g+ ear vein). A total Anal temperature was measured every 0.5 hours, for a total of 5 hours.
Result:
The different dosage groups of Xinbochaihuang Granules can reduce the body temperature of febrile New Zealand rabbits. The antipyretic effect of Chaihuang 1 group is obviously better than that of 2 or 3 groups.
Conclusion:
New Bo Chai Huang granule has obvious antipyretic effect on endotoxin induced fever in New Zealand rabbits.
The second part is the effect of Xin Bo Chai Huang Granule on endogenous pyrogen in serum and cerebrospinal fluid of rabbits with endotoxin induced fever.
background
Fever is a common symptom of various clinical diseases. Its mechanism is mainly produced by exogenous pyrogen in mononuclear macrophages and releasing EP in vivo. In recent years, EP includes IL-1 beta (IL-1 beta), tumor necrosis factor - alpha (TNF- alpha), interferon (IFN), macrophage macrophage inflammatory protein -1 (MIP-1), IL-6, etc. EP directly or indirectly sent fever information. The hypothalamus and hypothalamus release heat medium and cause fever.
Objective:
To study the effect of Xinbochaihuang granules on endogenous pyrogen in endotoxin-induced fever New Zealand rabbits, and further elucidate the Antipyretic Mechanism of Xinbochaihuang granules.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid was injected with endotoxin 0.3ug/kg from the vein of Chai Huang 4g+ ear, and the 3 groups of Chai Huang (shinhuang Chai Huang liquid 10ml/kg combined with endotoxin 0.3ug/kg injected with Chai Huang 2g+ ear vein). The rectal temperature was measured every 0.5 hours for 5 hours, and the serum and the interleukin -1 beta (IL-1 beta) in cerebrospinal fluid was measured by radioimmunoassay (RIA), and the serum level of serum and cerebrospinal fluid (IL-1 beta) was measured by radioimmunoassay (RIA). The content of tumor necrosis factor - alpha (TNF- - a) and interleukin -6 (IL-6), and the correlation analysis of the inhibition rate of temperature change in 3 doses of Chai Huang and the inhibition rate of IL-1 beta, TNF- alpha and IL-6 content.
Result:
Different dosage groups of Xin Bo Chai Huang granule have the effect of reducing fever of New Zealand rabbits, reducing the content of IL-1 beta, TNF- A and IL-6 in cerebrospinal fluid and serum. The antipyretic effect of Chai Huang 1 groups is obviously better than that of 2 or 3 groups. There was a positive correlation between the inhibition rate of IL-1, IL-6 and TNF- alpha in CSF (P0.05).
Conclusion:
1. Xinbochaihuang Granules can significantly reduce endogenous pyrogen IL-1beta, TNF-alpha and IL-6 in blood and cerebrospinal fluid of New Zealand rabbits with endotoxin-induced fever.
2. The Antipyretic Mechanism of Xinbochaihuang granules may be related to the reduction of endogenous pyrogen IL-1beta, TNF-a and IL-6 in blood and cerebrospinal fluid.
The third part is the effect of Xin Bo Chai Huang Granule on the CSF and hypothalamic central fever mediators of endotoxin induced fever in New Zealand rabbits.
Background:
Fever is a complex process of participation and interaction of multiple factors. The mechanism is that heat activator acts on the production and release of endogenous pyrogen (EP) in certain cells. EP acts in the hypothalamus to produce central heating medium. The central heating medium reacts on the pivot of the body temperature adjustment, increases heat production, decreases heat dissipation, and body temperature. Inhibiting or blocking EP and/or central heating medium can produce antipyretic effect, which can prevent and cure the rise of body temperature or decrease the body temperature.
The central fever mediators are known as adrenocorticotropin releasing hormone (CRH), prostaglandin E2 (PGE2), arginine vasopressin (AVP) and melanocyte stimulating hormone (alpha -MSH).
Objective:
The effect of Xin Bo Chai Huang Granule on the cerebrospinal fluid and central fever medium in the hypothalamus caused by endotoxin induced heat in New Zealand rabbit model was studied, and the mechanism of antipyretic action of Xin Bo Chai Huang granule was further elucidated.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid was injected with endotoxin 0.3ug/kg (endotoxin 0.3ug/kg) with Chai Huang 4g+ ear vein, and 3 groups of Chai Huang (Chai Huang Chai Huang liquid 10ml/kg, which contained Chai Huang 2g+ ear vein injection endotoxin 0.3ug/kg). The rectal temperature was measured once every 0.5 hours, for 5 hours, and radioimmunoassay (RIA) was used to determine the prostaglandin E2 (PGE2) in the cerebrospinal fluid and the hypothalamus tissue of the hypothalamus (PGE2). The temperature change inhibition rates of PGE2 and AVP in three dose groups of Chaihuang were analyzed.
Result:
The effect of reducing PGE2 in cerebrospinal fluid and hypothalamus and increasing the content of AVP in cerebrospinal fluid and hypothalamus. The antipyretic effect of Chai Huang 1 groups was obviously better than that of 2 or 3 groups. There was a positive correlation between inhibition rate and the inhibition rate of PGE2 content change in 1H, 3h New Zealand rabbits' cerebrospinal fluid and hypothalamus (P0.05). There was a negative correlation between the inhibition rate of AVP content in the 3H cerebrospinal fluid and the hypothalamus after heat induced (P0.05).
Conclusion:
1. the effect of new Bo Chai Huang Granule on PGE2 and AVP in cerebrospinal fluid and hypothalamus of rabbits with endotoxin induced fever was significantly affected.
2. The Antipyretic Mechanism of Xinbochaihuang granules may be related to the decrease of PGE2 and the increase of AVP.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285;R720.597
本文编号：2171733
[Abstract]:Part one: the antipyretic effect of Xin Bo Chai Huang Granule on endotoxin induced fever in New Zealand rabbits.
background
Fever is a common clinical symptom. It is a complex process involving multiple links and multiple factors. It can inhibit or block some parts of the fever process to produce antipyretic effect and achieve the purpose of preventing temperature rise or lowering body temperature.
The main components of Xin Bo Chai Huang granules are baicalin and [1], bupleurum and scutellaria are the core drugs of ancient Xiao Chaihu soup "reconciliation Shaoyang", which are widely used in the clinical application of [2]. Xin Bo Chai Huang granules. The Antipyretic Mechanism of Xin Bo Chai Huang granules is not clear, and it needs further study.
Objective:
To study the antipyretic effect of Xin Bo Chai Huang Granule on endotoxin induced fever in New Zealand rabbits.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid containing the injection of endotoxin 0.3ug/kg in the vein of Chai Huang 4g+ ear, and 3 groups of Chai Huang (Chai Huang Chai Huang liquid 10ml/kg, including endotoxin 0.3ug/kg injected with Chai Huang 2g+ ear vein). A total Anal temperature was measured every 0.5 hours, for a total of 5 hours.
Result:
The different dosage groups of Xinbochaihuang Granules can reduce the body temperature of febrile New Zealand rabbits. The antipyretic effect of Chaihuang 1 group is obviously better than that of 2 or 3 groups.
Conclusion:
New Bo Chai Huang granule has obvious antipyretic effect on endotoxin induced fever in New Zealand rabbits.
The second part is the effect of Xin Bo Chai Huang Granule on endogenous pyrogen in serum and cerebrospinal fluid of rabbits with endotoxin induced fever.
background
Fever is a common symptom of various clinical diseases. Its mechanism is mainly produced by exogenous pyrogen in mononuclear macrophages and releasing EP in vivo. In recent years, EP includes IL-1 beta (IL-1 beta), tumor necrosis factor - alpha (TNF- alpha), interferon (IFN), macrophage macrophage inflammatory protein -1 (MIP-1), IL-6, etc. EP directly or indirectly sent fever information. The hypothalamus and hypothalamus release heat medium and cause fever.
Objective:
To study the effect of Xinbochaihuang granules on endogenous pyrogen in endotoxin-induced fever New Zealand rabbits, and further elucidate the Antipyretic Mechanism of Xinbochaihuang granules.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid was injected with endotoxin 0.3ug/kg from the vein of Chai Huang 4g+ ear, and the 3 groups of Chai Huang (shinhuang Chai Huang liquid 10ml/kg combined with endotoxin 0.3ug/kg injected with Chai Huang 2g+ ear vein). The rectal temperature was measured every 0.5 hours for 5 hours, and the serum and the interleukin -1 beta (IL-1 beta) in cerebrospinal fluid was measured by radioimmunoassay (RIA), and the serum level of serum and cerebrospinal fluid (IL-1 beta) was measured by radioimmunoassay (RIA). The content of tumor necrosis factor - alpha (TNF- - a) and interleukin -6 (IL-6), and the correlation analysis of the inhibition rate of temperature change in 3 doses of Chai Huang and the inhibition rate of IL-1 beta, TNF- alpha and IL-6 content.
Result:
Different dosage groups of Xin Bo Chai Huang granule have the effect of reducing fever of New Zealand rabbits, reducing the content of IL-1 beta, TNF- A and IL-6 in cerebrospinal fluid and serum. The antipyretic effect of Chai Huang 1 groups is obviously better than that of 2 or 3 groups. There was a positive correlation between the inhibition rate of IL-1, IL-6 and TNF- alpha in CSF (P0.05).
Conclusion:
1. Xinbochaihuang Granules can significantly reduce endogenous pyrogen IL-1beta, TNF-alpha and IL-6 in blood and cerebrospinal fluid of New Zealand rabbits with endotoxin-induced fever.
2. The Antipyretic Mechanism of Xinbochaihuang granules may be related to the reduction of endogenous pyrogen IL-1beta, TNF-a and IL-6 in blood and cerebrospinal fluid.
The third part is the effect of Xin Bo Chai Huang Granule on the CSF and hypothalamic central fever mediators of endotoxin induced fever in New Zealand rabbits.
Background:
Fever is a complex process of participation and interaction of multiple factors. The mechanism is that heat activator acts on the production and release of endogenous pyrogen (EP) in certain cells. EP acts in the hypothalamus to produce central heating medium. The central heating medium reacts on the pivot of the body temperature adjustment, increases heat production, decreases heat dissipation, and body temperature. Inhibiting or blocking EP and/or central heating medium can produce antipyretic effect, which can prevent and cure the rise of body temperature or decrease the body temperature.
The central fever mediators are known as adrenocorticotropin releasing hormone (CRH), prostaglandin E2 (PGE2), arginine vasopressin (AVP) and melanocyte stimulating hormone (alpha -MSH).
Objective:
The effect of Xin Bo Chai Huang Granule on the cerebrospinal fluid and central fever medium in the hypothalamus caused by endotoxin induced heat in New Zealand rabbit model was studied, and the mechanism of antipyretic action of Xin Bo Chai Huang granule was further elucidated.
Method:
90 New Zealand rabbits were randomly divided into the control group (the saline 10ml/kg+ of the gavage saline 0.3ug/kg) and the fever group (intragastric saline 10ml/kg+ auricular vein injection of endotoxin 0.3ug/kg), and the group of Chai Huang (gavage Xin Bo Chai Huang liquid 10ml/kg containing Chai Huang 8g+ ear vein intravenous endotoxin 0.3ug/kg); 2 groups of Chai Huang (gavage new Bo) The 10ml/kg of Chai Huang liquid was injected with endotoxin 0.3ug/kg (endotoxin 0.3ug/kg) with Chai Huang 4g+ ear vein, and 3 groups of Chai Huang (Chai Huang Chai Huang liquid 10ml/kg, which contained Chai Huang 2g+ ear vein injection endotoxin 0.3ug/kg). The rectal temperature was measured once every 0.5 hours, for 5 hours, and radioimmunoassay (RIA) was used to determine the prostaglandin E2 (PGE2) in the cerebrospinal fluid and the hypothalamus tissue of the hypothalamus (PGE2). The temperature change inhibition rates of PGE2 and AVP in three dose groups of Chaihuang were analyzed.
Result:
The effect of reducing PGE2 in cerebrospinal fluid and hypothalamus and increasing the content of AVP in cerebrospinal fluid and hypothalamus. The antipyretic effect of Chai Huang 1 groups was obviously better than that of 2 or 3 groups. There was a positive correlation between inhibition rate and the inhibition rate of PGE2 content change in 1H, 3h New Zealand rabbits' cerebrospinal fluid and hypothalamus (P0.05). There was a negative correlation between the inhibition rate of AVP content in the 3H cerebrospinal fluid and the hypothalamus after heat induced (P0.05).
Conclusion:
1. the effect of new Bo Chai Huang Granule on PGE2 and AVP in cerebrospinal fluid and hypothalamus of rabbits with endotoxin induced fever was significantly affected.
2. The Antipyretic Mechanism of Xinbochaihuang granules may be related to the decrease of PGE2 and the increase of AVP.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285;R720.597
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