【摘要】：第一部分新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔的解熱作用 背景 發(fā)熱是一種臨床上的常見癥狀，是一個(gè)含有多個(gè)環(huán)節(jié)、由多個(gè)因素共同參與的復(fù)雜過程，抑制或阻斷發(fā)熱過程中的某些環(huán)節(jié)可產(chǎn)生解熱效應(yīng)，達(dá)到防治體溫升高或降低體溫的目的。 新博柴黃顆粒的主要成分為黃芩苷和柴胡苷[1]，柴胡、黃芩是古方小柴胡湯“和解少陽”的核心藥對(duì)[2]。新博柴黃顆粒在臨床應(yīng)用廣泛，解熱效果顯著，但是新博柴黃顆粒的解熱機(jī)制尚不清楚，需進(jìn)一步的研究。 目的: 研究新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔模型的解熱作用。 方法: 90只新西蘭兔，隨機(jī)分為對(duì)照組（灌胃生理鹽水10ml/kg+耳緣靜脈注射生理鹽水0.3ug/kg）；發(fā)熱組（灌胃生理鹽水10ml/kg+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃1組（灌胃新博柴黃液10ml/kg共含柴黃8g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃2組（灌胃新博柴黃液10ml/kg共含柴黃4g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃3組（灌胃新博柴黃液10ml/kg共含柴黃2g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）。每0.5小時(shí)測(cè)量肛溫一次，共5小時(shí)。 結(jié)果: 新博柴黃顆粒不同劑量組均具有降低發(fā)熱新西蘭兔體溫的作用，柴黃1組解熱作用明顯優(yōu)于2或3組。 結(jié)論: 新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔有明顯的解熱作用。 第二部分新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔血清、腦脊液中內(nèi)生致熱原的影響 背景 發(fā)熱是臨床上多種疾病的常見癥狀，其機(jī)制主要為外源性致熱原作用于體內(nèi)單核巨噬細(xì)胞產(chǎn)生并釋放EP,近年來發(fā)現(xiàn)的EP包括白介素(IL-1β)、腫瘤壞死因子-α(TNF-α)、干擾素(IFN)、巨噬細(xì)胞炎癥蛋白-1(MIP-1)、IL-6等,EP將發(fā)熱信息直接或間接送達(dá)下丘腦,下丘腦釋放發(fā)熱介質(zhì)引起發(fā)熱。 目的： 研究新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔模型內(nèi)生致熱原的影響,進(jìn)一步闡明新博柴黃顆粒的解熱作用機(jī)制。 方法: 90只新西蘭兔，隨機(jī)分為對(duì)照組（灌胃生理鹽水10ml/kg+耳緣靜脈注射生理鹽水0.3ug/kg）；發(fā)熱組（灌胃生理鹽水10ml/kg+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃1組（灌胃新博柴黃液10ml/kg共含柴黃8g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃2組（灌胃新博柴黃液10ml/kg共含柴黃4g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃3組（灌胃新博柴黃液10ml/kg共含柴黃2g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）。每0.5小時(shí)測(cè)量肛溫一次，共5小時(shí)，用放射免疫法（RIA）測(cè)定兩個(gè)發(fā)熱高峰血清及腦脊液中白細(xì)胞介素-1β(IL-1β)、腫瘤壞死因子-α(TNF-α)和白細(xì)胞介素-6(IL-6)含量。并將柴黃3個(gè)劑量組的溫度變化抑制率與IL-1β、TNF-α、IL-6含量變化抑制率分別作相關(guān)性分析。 結(jié)果: 新博柴黃顆粒不同劑量組均具有降低發(fā)熱新西蘭兔體溫的作用，具有降低腦脊液及血清中IL-1β、TNF-α和IL-6含量作用。柴黃1組解熱作用明顯優(yōu)于2或3組。相關(guān)分析表明，新博柴黃顆粒對(duì)新西蘭兔的體溫變化抑制率與致熱后1h、3h新西蘭兔血清、腦脊液中IL-1β、IL-6、TNF-α含量變化抑制率之間呈正相關(guān)(P0.05)。 結(jié)論: 1.新博柴黃顆�？擅黠@降低內(nèi)毒素致熱新西蘭兔血液及腦脊液中的內(nèi)生致熱原IL-1β、TNF-α和IL-6； 2.新博柴黃顆粒的解熱作用機(jī)制可能與減少血液及腦脊液中內(nèi)生致熱原IL-1β、TNF-α和IL-6的含量有關(guān)。 第三部分新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔腦脊液、下丘腦中中樞性發(fā)熱介質(zhì)的影響 背景： 發(fā)熱是一個(gè)由多因子參與及相互作用的復(fù)雜過程，其機(jī)制為發(fā)熱激活物作用于某些細(xì)胞產(chǎn)生和釋放內(nèi)生致熱原(EP)， EP作用于下丘腦產(chǎn)生中樞性發(fā)熱介質(zhì)，中樞性發(fā)熱介質(zhì)再作用于體溫調(diào)節(jié)中樞使調(diào)定點(diǎn)上移，產(chǎn)熱增加，散熱減少，體溫上升，從而導(dǎo)致發(fā)熱。抑制或阻斷EP和/或中樞性發(fā)熱介質(zhì)可產(chǎn)生解熱效應(yīng)，達(dá)到防治體溫升高或降低體溫的目的。 現(xiàn)已知的中樞性發(fā)熱介質(zhì)包括促腎上腺皮質(zhì)激素釋放激素(CRH)、前列腺素E2(PGE2)、精氨酸加壓素(AVP)和黑素細(xì)胞刺激素(α-MSH)等。 目的： 研究新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔模型腦脊液、下丘腦中中樞性發(fā)熱介質(zhì)的影響,進(jìn)一步闡明新博柴黃顆粒的解熱作用機(jī)制。 方法: 90只新西蘭兔，隨機(jī)分為對(duì)照組（灌胃生理鹽水10ml/kg+耳緣靜脈注射生理鹽水0.3ug/kg）；發(fā)熱組（灌胃生理鹽水10ml/kg+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃1組（灌胃新博柴黃液10ml/kg共含柴黃8g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃2組（灌胃新博柴黃液10ml/kg共含柴黃4g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）；柴黃3組（灌胃新博柴黃液10ml/kg共含柴黃2g+耳緣靜脈注射內(nèi)毒素0.3ug/kg）。每0.5小時(shí)測(cè)量肛溫一次，共5小時(shí)，用放射免疫法（RIA）測(cè)定兩個(gè)發(fā)熱高峰腦脊液及下丘腦組織中前列腺素E2(PGE2)、精氨酸加壓素(AVP)含量。并將柴黃3個(gè)劑量組的溫度變化抑制率PGE2和AVP含量變化抑制率分別作相關(guān)性分析。 結(jié)果: 新博柴黃顆粒不同劑量組均具有降低發(fā)熱新西蘭兔體溫的作用，具有降低腦脊液和下丘腦中PGE2的作用，具有升高腦脊液和下丘腦中AVP含量的作用。柴黃1組解熱作用明顯優(yōu)于2或3組。相關(guān)分析表明，新博柴黃顆粒對(duì)新西蘭兔的體溫變化抑制率與致熱后1h、3h新西蘭兔腦脊液、下丘腦中PGE2含量變化抑制率之間呈正相關(guān)(P0.05)，與致熱后3h腦脊液、下丘腦中AVP含量變化抑制率之間呈負(fù)相關(guān)（P0.05）。 結(jié)論: 1.新博柴黃顆粒對(duì)內(nèi)毒素致熱新西蘭兔腦脊液和下丘腦中的PGE2、AVP產(chǎn)生明顯影響； 2.新博柴黃顆粒的解熱作用機(jī)制可能與減少中樞性正調(diào)節(jié)介質(zhì)PGE2，，增加中樞性負(fù)調(diào)節(jié)介質(zhì)AVP有關(guān)。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R285;R720.597

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