本文選題：惡病質(zhì) + 表沒食子兒茶素沒食子酸酯　； 參考：《福建醫(yī)科大學》2013年碩士論文

【摘要】：目的 觀察表沒食子兒茶素沒食子酸酯(EGCG)、β-羥基-β甲基丁酸鹽(HMB)聯(lián)合應用對小鼠癌癥惡病質(zhì)的治療作用。并初步探討藥物發(fā)揮作用的可能機制。 方法 接種小鼠結(jié)腸腺癌Colon26(C26)細胞的雄性BALB/C小鼠前腋窩皮下，9天后癌癥惡病質(zhì)模型基本建立。40只小鼠隨機分為5組：A組空白對照組、B組荷瘤安慰劑（生理鹽水）對照組、C組EGCG治療組、D組HMB治療組、E組聯(lián)合治療組,每組8只。每天按時監(jiān)測小鼠食物攝入量，小鼠體質(zhì)量及腫瘤體積。第16天，記錄小鼠右側(cè)腓腸肌重量和去瘤體重，檢測血生化指標、血清白細胞介素-6(IL-6)、腫瘤壞死因子-ɑ(TNF-α)、C-反應性蛋白（CRP）水平，并用免疫組織化學法檢測腫瘤組織核因子-κB(NF-κB)表達、熒光定量PCR腓腸肌MAFbx及MURF-1基因的表達。 結(jié)果 1癌癥惡病質(zhì)模型的建立后四組小鼠皮下接種colon-26細胞4~5天后，腫瘤開始可以皮下觸及。1周后長至約0.5cm3大小，小鼠開始出現(xiàn)毛色發(fā)暗、豎立、脫落和活動遲緩，活動減少、虛弱等表現(xiàn)。至第9天，，所有荷瘤小鼠的衰弱表現(xiàn)更加明顯，且與正常對照組相比體質(zhì)量顯著下降(p＜0.05)，即進入惡病質(zhì)狀態(tài)。 2體重變化及攝食量情況接種初始幾天各組間差異并無顯著性，荷瘤小鼠體質(zhì)量在第12天開始下降，且顯著低于正常小鼠體質(zhì)量（P＜0.05），到第16天降至最低，各組終末體質(zhì)量各組荷瘤小鼠組間差異無統(tǒng)計學意義（P＞0.05）。但去瘤體質(zhì)量荷瘤小鼠均顯著低于正常小鼠（P＜0.05）。各組間食物攝食量各組間無明顯差異（P＞0.05）。 3腫瘤體積變化荷瘤小鼠腫瘤從第5天開始可觸及，腫瘤體積從第9天開始增大迅速，且EGCG治療組、HMB治療組、聯(lián)合治療組較安慰劑治療組增長緩慢。至第16天各治療組顯著小于安慰劑治療組。 4腓腸肌質(zhì)量腓腸肌質(zhì)量EGCG治療組、HMB治療組、聯(lián)合治療組、安慰劑治療組與正常對照組間，EGCG治療組和HMB治療組與聯(lián)合治療組間的差異有統(tǒng)計學意義（P＜0.05），EGCG治療組與HMB治療組間的差異有統(tǒng)計學意義（P＜0.05）。 5血清生化指標的比較TP、ALB、Glu、TG水平EGCG治療組、HMB治療組、聯(lián)合治療組、安慰劑治療組與正常對照組間，EGCG治療組、HMB治療組、聯(lián)合治療組與安慰劑治療組間的差異有統(tǒng)計學意義（P＜0.05）。 6細胞因子(TNF-α、IL-6、CRP) EGCG治療組、HMB治療組、聯(lián)合治療組、安慰劑治療組與正常對照組間，EGCG治療組、HMB治療組，聯(lián)合治療組與安慰劑治療組間的差異均有統(tǒng)計學意義（P＜0.05）。EGCG治療組、HMB治療組和聯(lián)合治療組間的差異均有統(tǒng)計學意義（P＜0.05）。 7NF-κB表達水平的比較EGCG治療組、HMB治療組，聯(lián)合治療組與惡病質(zhì)對照組安慰劑治療組間的差異均有統(tǒng)計學意義（P＜0.05）。EGCG治療組、HMB治療組和聯(lián)合治療組間的差異均有統(tǒng)計學意義（P＜0.05）。 8MAFbx及MuRF-1的表達水平比較EGCG治療組、HMB治療組、聯(lián)合治療組、安慰劑治療組與正常對照組間，EGCG治療組、HMB治療組，聯(lián)合治療組與安慰劑治療組間的差異均有統(tǒng)計學意義(P＜0.05）。EGCG治療組、HMB治療組和聯(lián)合治療組間的差異均有統(tǒng)計學意義（P＜0.05）。 結(jié)論 1EGCG和HMB聯(lián)合療效優(yōu)于單一用藥。 2可能通過抑制NF-κB，改善骨骼肌代謝，治療癌癥惡病質(zhì)。
[Abstract]:objective
To observe the therapeutic effect of the combination of epigallocatechin gallate (EGCG) and beta hydroxy beta methylbutyrate (HMB) on cancer cachexia in mice, and to explore the possible mechanism of the effect of the drug.
Method
The male BALB/C mice of the colon adenocarcinoma Colon26 (C26) cells were subcutaneously inoculated into the anterior armpit of the male BALB/C mice. After 9 days, the cancer cachexia model was randomly divided into 5 groups: the A group blank control group, the B group, the placebo (physiological saline) control group, the C group EGCG treatment group, the D group HMB treatment group, and the E group combined treatment group, 8 in each group. Every day was monitored on time. Mice food intake, body mass and tumor volume. Sixteenth days, the weight of the right gastrocnemius and tumor weight were recorded, blood biochemical indexes, serum interleukin -6 (IL-6), tumor necrosis factor (TNF- alpha), C- reactive protein (CRP), and the expression of nuclear factor kappa B (NF- kappa B) in tumor tissues were detected by immunohistochemistry. The expression of MAFbx and MURF-1 genes in gastrocnemius muscle was quantified by PCR.
Result
1 after the establishment of the 1 cachexia model, four groups of mice were subcutaneously inoculated with Colon-26 cells for 4~5 days. The tumor began to grow subcutaneously to about 0.5cm3 after.1 weeks, and the mice began to appear darkening, erect, shedding, slow activity, activity decrease, weakness and so on. To ninth days, the decline of all tumor bearing mice was more obvious and positive. The body weight of the control group was significantly lower than that of the control group (P < 0.05), that is, entering cachexia.
2 the difference of weight change and feeding amount was not significant in the first few days. The body mass of the tumor bearing mice began to decrease at the beginning of twelfth days, and significantly lower than normal mice body mass (P < 0.05), and to the lowest level in sixteenth days. There was no significant difference between the groups of all groups of end body mass bearing tumor bearing mice (P > 0.05). Tumor mice were significantly lower than normal mice (P < 0.05). There was no significant difference in food intake among groups (P > 0.05).
3 tumor volume changes were palpable in the tumor bearing mice from fifth days. The tumor volume began to increase rapidly from the ninth day, and the EGCG treatment group, the HMB treatment group, the combined treatment group increased slowly compared with the placebo group. To sixteenth days, the treatment group was significantly smaller than the placebo treatment group.
4 gastrocnemius mass of gastrocnemius mass EGCG treatment group, HMB treatment group, combined treatment group, placebo group and normal control group, EGCG treatment group and HMB treatment group and the joint treatment group differences were statistically significant (P < 0.05), EGCG treatment group and HMB treatment group differences were statistically significant (P < 0.05).
5 Comparison of serum biochemical indexes: TP, ALB, Glu, TG level EGCG treatment group, HMB treatment group, combined treatment group, placebo treatment group and normal control group, EGCG treatment group, HMB treatment group, the difference between the combined treatment group and the placebo group was statistically significant (P < 0.05).
6 cell factor (TNF-, IL-6, CRP) EGCG treatment group, HMB treatment group, combined treatment group, placebo treatment group and normal control group, EGCG treatment group, HMB treatment group, the difference between the combined treatment group and the placebo treatment group were statistically significant (P < 0.05).EGCG treatment group, HMB treatment group and the joint treatment group differences were statistically significant ( P < 0.05).
The comparison of the expression level of 7NF- kappa B was statistically significant between the EGCG treatment group, the HMB treatment group, the combined treatment group and the cachexia control group (P < 0.05).EGCG treatment group, and the difference between the HMB treatment group and the combined treatment group had statistical significance (P < 0.05).
The expression level of 8MAFbx and MuRF-1 was compared between the EGCG treatment group, the HMB treatment group, the combined treatment group, the placebo treatment group and the normal control group, the EGCG treatment group, the HMB treatment group, the difference between the combined treatment group and the placebo group were statistically significant (P < 0.05).EGCG treatment group, the difference between the HMB treatment group and the combined treatment group was statistically significant. Significance (P < 0.05).
conclusion
The combination of 1EGCG and HMB was better than a single drug.
2, it is possible to improve the metabolism of skeletal muscle and cure cancer cachexia by inhibiting NF- kappa B.

【學位授予單位】：福建醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R73-3

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相關(guān)期刊論文 前1條

1 趙艷鳳;姜達;;癌性惡病質(zhì)發(fā)生的分子機制及其逆轉(zhuǎn)[J];實用腫瘤學雜志;2007年02期

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