本文選題：人參皂苷Rg1　切入點(diǎn)：胰島素生長(zhǎng)因子-1　出處：《青島大學(xué)》2014年碩士論文

【摘要】：人參皂苷Rgl (ginsenoside Rgl)是人參主要的活性成分,具有神經(jīng)營(yíng)養(yǎng)和神經(jīng)保護(hù)作用。胰島素樣生長(zhǎng)因子-1(insulin-like growth factor1, IGF-1)是腦內(nèi)非常重要的生長(zhǎng)因子,可以促進(jìn)神經(jīng)元的分化和存活。機(jī)制研究顯示Rgl與IGF-Ⅰ的神經(jīng)保護(hù)作用均與IGF-I受體(IGF-R)信號(hào)途徑有關(guān),但二者合用是否具有協(xié)同作用,尚不清楚。本實(shí)驗(yàn)應(yīng)用6-羥基多巴(6-hydroxydopamine,6-OHDA)損傷多巴胺能神經(jīng)元細(xì)胞系SK-N-SH細(xì)胞,建立帕金森病(Parkinson's disease,PD)細(xì)胞模型,神經(jīng)毒素1-甲基-4-苯基-1,2,3,6-四氫吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)制備的PD小鼠模型,應(yīng)用MTT法、免疫組織化學(xué)染色法、高效液相色譜法及免疫印跡法等多種評(píng)價(jià)方法,探討人參皂苷Rg1、IGF-1及二者合用對(duì)多巴胺能神經(jīng)元的保護(hù)作用及其可能機(jī)制。實(shí)驗(yàn)結(jié)果如下： 1.IGF-1可劑量依賴式對(duì)抗6-OHDA對(duì)SK-N-SH細(xì)胞的損傷(P0.05)。Rg1與IGF-1合用具有協(xié)同作用(P0.05)。 2.6-OHDA能夠明顯降低Bcl-2蛋白表達(dá)(P0.05)。Rg1、IGF-1及二者合用均可逆轉(zhuǎn)上述變化,且Rgl與IGF-1合用組作用最明顯(P0.05)。 3.6-OHDA可明顯升高Bax蛋白表達(dá)(P0.05)。Rg1、IGF-1及二者合用均可逆轉(zhuǎn)上述變化(P0.01。 Rg1與IGF-1合用組與單用組相比,無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 4. MPTP可明顯降低小鼠紋狀體DA及其代謝產(chǎn)物DOPAC, HVA的含量,IGF-1(0.1μg/μl,0.5μg/μl,1μg/μl)能夠?qū)筂PTP的毒性作用,其中0.5μg/μl IGF-1神經(jīng)保護(hù)作用最為明顯(P0.05)。 5. Rg1、IGF-1及二者合用均可以明顯增加DA及其代謝產(chǎn)物DOPAC, HVA含量,與MPTP組相比,差異顯著。且Rgl與IGF-1二者合用的效果最為明顯(P0.05)。 6. MPTP可明顯減少小鼠黑質(zhì)酪氨酸羥化酶免疫陽(yáng)性(TH-IR)神經(jīng)元數(shù)目。Rg1、IGF-1及二者合用均可明顯增加TH-IR神經(jīng)元的數(shù)目,且以二者合用組的作用最為顯著(P0.05)。 7. MPTP可明顯減少小鼠黑質(zhì)抗凋亡蛋白Bcl-2的表達(dá),增加促凋亡蛋白Bax的表達(dá)。Rg1、IGF-1及二者合用均可明顯逆轉(zhuǎn)上述變化,且以二者合用的效果最為明顯(P0.05)。 上述結(jié)果表明Rg1、IGF-1及二者合用均能夠?qū)股窠?jīng)毒素對(duì)DA神經(jīng)元的毒性作用,且Rg1與IGF-1合用具有協(xié)同作用。本研究為PD的預(yù)防與治療開(kāi)辟了新的途徑,提供了新的實(shí)驗(yàn)依據(jù)。
[Abstract]:Ginsenoside Rgl (ginsenoside Rgl) is the main active ingredient of ginseng, has neuroprotective effect of insulin-like growth factor -1 (insulin-like growth factor1, IGF-1) is an important growth factor in the brain, can promote neuronal differentiation and survival mechanisms. Studies show neuroprotective effect of Rgl and IGF- I were with the IGF-I receptor (IGF-R) pathway, but the combination of the two will have a synergistic effect, is not clear. The experiment used 6- 6-hydroxydopamine (6-hydroxydopamine, 6-OHDA) SK-N-SH cell injury of dopaminergic neuronal cell lines, the establishment of Parkinson's disease (Parkinson's disease, PD) cell model of neurotoxin 1- methyl -4- phenyl -1,2,3,6- tetrahydropyridine four (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) PD mice model preparation, using MTT method, immunohistochemistry, immune method and high performance liquid chromatography A variety of evaluation methods of imprinting, ginsenoside Rg1, IGF-1 and the combination of the two protective effect on dopaminergic neurons and its possible mechanism. The experimental results are as follows:
1.IGF-1 in a dose-dependent manner against 6-OHDA injury in SK-N-SH cells (P0.05) of.Rg1 and IGF-1 has a synergistic effect (P0.05).
2.6-OHDA can decrease the expression of Bcl-2 (P0.05).Rg1, IGF-1 and the combination of the two can reverse these changes, and the Rgl and IGF-1 group had significant effect (P0.05).
3.6-OHDA can significantly increase the expression of Bax (P0.05).Rg1, IGF-1 and the combination of the two can reverse the above changes (P0.01. Rg1 combined with IGF-1 group and single group compared with no statistical significance (P0.05).
4. MPTP can significantly reduce the mouse striatal DA and its metabolites DOPAC, HVA content, IGF-1 (0.1 g/ L, 0.5 g/ L, 1 g/ L) to cytotoxicity against MPTP, of which 0.5 mu g/ Mu L IGF-1 neuroprotective effect was most significant (P0.05).
5. Rg1, IGF-1 and the combination of the two can significantly increase DA and its metabolites DOPAC, HVA content, compared with group MPTP. And the Rgl and IGF-1 combination of the two has the most obvious effect (P0.05).
6. MPTP could significantly reduce the tyrosine hydroxylase positive neurons in mice (TH-IR) the number of.Rg1, IGF-1 and the combination of the two can obviously increase the number of TH-IR neurons, and the combination of the two group is the most significant (P0.05).
7. the expression of MPTP can significantly reduce the anti apoptotic protein Bcl-2 in substantia nigra of mice, increase the expression of.Rg1 apoptosis protein Bax, IGF-1 and the combination of the two can be significantly reversed these changes, and the combined effect of the two most obvious (P0.05).
The results showed that Rg1, IGF-1 and the combination of the two can be toxic effect against the neurotoxin on DA neurons, and Rg1 combined with IGF-1 has a synergistic effect. This study provides a new way for the prevention and treatment of PD, provides a new experimental basis.

【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742.5

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