CN110269936A - A kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation - Google Patents

A kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation Download PDF

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CN110269936A
CN110269936A CN201810213285.5A CN201810213285A CN110269936A CN 110269936 A CN110269936 A CN 110269936A CN 201810213285 A CN201810213285 A CN 201810213285A CN 110269936 A CN110269936 A CN 110269936A
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gold nanorods
gold
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肖湘衡
叶天宇
余锂镭
蒋昌忠
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SUZHOU INSTITUTE OF WUHAN UNIVERSITY
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Abstract

The invention discloses a kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation, utilize hydro-thermal method, the length of gold nanorods is adjusted by adjusting the amount of silver ion respectively, adjusts the diameter of gold nanorods by the amount for adjusting gold nano seed liquor, accurate control obtains the gold nanorods that longitudinal plasma absorption peak matches near 808nm, with near-infrared laser wavelength.By gold nanorods surface with the polyethyleneglycol modified of sulfydryl, its bio-toxicity is reduced.Gold nanorods after modification are injected into inside Left Stellate Ganglions, under the irradiation of 808nm near-infrared laser, gold nanorods after modification, which generate heat, increases Left Stellate Ganglions temperature, inhibit ganglionic activity, its function is reduced, Left Stellate Ganglions inhibitor provided by the invention is expected to reach prevention and treatment ventricular arrhythmia.

Description

A kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation
Technical field
The invention belongs to nano material field of medical applications, are related to a kind of starlike mind in left side based on near-infrared laser irradiation Warp knuckle inhibitor.
Background technique
Due between conduction band electronics and light interaction cause their collective oscillation, gold nano grain is acknowledged as very Promising nano material.Local surface plasma resonance (LSPRS) will receive the structure, form, size of nano material with And the strong influence of surrounding medium.The photoelectric properties and physicochemical property of the gold nano grain not only serious ruler depending on them It is very little, their form is also depended on, therefore the form for controlling gold nano grain becomes extremely important.Compared to spherical gold nano grain For, gold nanorods have more controllability and applicability, since it has unique optical plasma characteristic, in sensing, table Face enhancing Raman scattering (SERS), catalysis and photo-thermal therapy etc. show huge application potential.
Due to the anisotropy of gold nanorods shape, plasma resonance can be carried out by adjusting shape and draw ratio and is inhaled Peak is received to be regulated and controled.The method for much synthesizing the gold nanorods of controllable draw ratio has been developed at present.Generally speaking, mainly have three Kind preparation method: electrochemical process, ultraviolet light irradiate the growth method that photoreduction met hod and seed mediate.Wherein, the growth that seed mediates Method is since its process is simple, and the draw ratio and product of easily controllable gold nanorods are with the uniformity of height and further table The flexibility of face modification, seed growth becomes synthesis gold nanorods method the most popular, extensive by many research groups Using.Although the gold nano grain of many different-shapes has been investigated, in terms of the system regulation of gold nanorods It studies still more poor.
Arrhythmia cordis occur in neuromodulation mechanism be the research of current cardiac electrophysiology hot issue, nerve intervene also by Gradually become one of the means for the treatment of irregular heart pulse.Stellate ganglion (stellate ganglion) is that sympathetic nerve leads to heart Important access, it is excitatoty variation it is closely related with the generation of arrhythmia cordis.Once there is related report, and improved stellate ganglion Temperature can inhibit its excitability, due to gold nanorods longitudinal surface plasma absorption peak have height controllability, There is very extensive application in terms of Photo-thermal technology application.But inhibit Left Stellate Ganglions using gold nanorods Photothermal characterisation Research it is less.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of Left Stellate Ganglions suppressions based on near-infrared laser irradiation Preparation, the main component of this neuromere inhibitor are the gold nanorods of surface modification sulfydryl, the absorption peak of this gold nanorods In 808nm.The present invention also provides one kind accurately to prepare absorption peak in the method for the gold nanorods of 808nm.A left side provided by the invention Side stellate ganglion inhibitor mainly inhibits left side of heart star in the Photothermal characterisation of 808nm gold nanorods using absorption peak Shape neuromere activity is expected to become the new strategy of prevention and treatment malignant ventricular arrhythmia cordis.
Strategy of the invention is as follows: utilize hydro-thermal method, respectively by adjust the amount adjusting gold nanorods of silver ion length, Amount by adjusting gold nano seed liquor adjusts the diameter of gold nanorods, and accurate control obtains matching with near-infrared laser wavelength Gold nanorods, reach strongest photothermal conversion efficiency, improve Left Stellate Ganglions using the heat that gold nanorods generate Temperature, to inhibit ganglionic activity and function, to achieve the effect that prevent and treat malignant ventricular arrhythmia cordis.
Technical solution provided by the invention are as follows:
A kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation, is prepared by the following method to obtain:
(1) at 25-30 DEG C, the chlorauric acid solution that concentration is 0.05M is added in the CTAB aqueous solution that concentration is 0.1M, with The speed of 1200rpm stirs, and the concentration that ice water is prepared is the NaBH of 0.01M4Solution is added in above-mentioned solution, continues to stir 2min is until solution becomes brown color to get gold nano seed liquor is arrived；It is standby that gold nano seed liquor is saved to 2h at 25-30 DEG C With；Wherein, chlorauric acid solution, CTAB aqueous solution, NaBH4The volume ratio of solution is 1:200:12；
(2) at 25-30 DEG C, the chlorauric acid solution that concentration is 0.05M is added in the CTAB aqueous solution that concentration is 0.1M, so The silver nitrate solution that concentration is 0.01M is added afterwards, is uniformly mixed, then it is 0.1M's that the concentration newly prepared is added into mixed solution L-AA solution mixes, growth solution is made；It is stirred under the conditions of 25-30 DEG C, growth solution is become from faint yellow It is colourless；Then salt acid for adjusting pH value is added to 2；Then 30 μ L gold nano seed liquors are added, 12h is stored at room temperature after mixing, are centrifuged, Washing, be absorbed peak 808nm gold nanorods；Wherein, chlorauric acid solution, CTAB aqueous solution, silver nitrate solution, L- are anti-bad Hematic acid solution, gold nano seed liquor volume ratio be 20:2000:20:16:3；
(3) modify gold nanorods: in deionized water, band mercapto is added in the gold nanorods ultrasonic disperse that step (2) is obtained The polyethylene glycol of base, mechanical oscillation 0.5h, is placed at room temperature for 12h, and the gold nanorods of surface modification sulfydryl can be obtained；
(4) will to be dispersed in again phosphate-buffered salt after the gold nanorods centrifugation of surface modification sulfydryl that step (3) obtains molten To get to the Left Stellate Ganglions inhibitor that is irradiated based on near-infrared laser in liquid.
The concentration that step (1) obtains Au in gold nano seed liquor is 2.5 × 10-6M。
The concentration of the gold nanorods of surface modification sulfydryl is 80 μ g/mL in step (4).
Magnetic agitation can be used in step (1), revolving speed is set as 1200rpm, at least needs before the use of gold nano seed liquor 1h is stood, so as to NaBH extra in gold nano seed liquor4It decomposes complete.
Centrifugal rotational speed is 9000rpm, centrifugation time 10min in step (2) and step (4).
Reaction temperature is between 25 DEG C to 30 DEG C in the present invention, and temperature is lower than 25 DEG C, and CTAB can be recrystallized.
The present invention controls gold nano using the additive amount of gold nano seed liquor using the length of silver ion control gold nanorods The diameter of stick can obtain continuously adjustable gold nanorods etc. by two methods with the draw ratio of the control gold nanorods of system Gas ions absorption peak, available required absorption peak is in the gold nanorods of 808nm, and after surface modification, gold nanorods disperse Property it is higher, be injected into Left Stellate Ganglions, near-infrared laser irradiation is not it can be found that the nerve of gold nanorods is injected in comparison Section, the neuromere temperature for injecting gold nanorods is significantly raised, finds that the function of Left Stellate Ganglions is obvious by electro photoluminescence It is suppressed, can achieve the effect of prevention and treatment malignant ventricular arrhythmia cordis.
Left Stellate Ganglions inhibitor provided by the invention uses the gold nanorods of surface modification sulfydryl, makes it have more High dispersibility and lower bio-toxicity.
Detailed description of the invention
Fig. 1 is that the SEM of 1 different length gold nanorods of embodiment schemes；Wherein, Fig. 1 (a), Fig. 1 (b), Fig. 1 (c), Fig. 1 (d), Fig. 1 (e), Fig. 1 (f) successively represent the SEM figure that the gold nanorods prepared as 1,2,3,4,5,6 solution are numbered in embodiment 1.
Fig. 2 is the ultraviolet-visible absorption spectroscopy of 1 different length gold nanorods of embodiment；Wherein, a, b, c, d, e, f successively generation The ultraviolet-visible absorption spectroscopy of the gold nanorods for the solution preparation that number is 1,2,3,4,5,6 in table embodiment 1.
Fig. 3 is the SEM picture of 2 different-diameter gold nanorods of embodiment；Wherein, Fig. 3 (a), Fig. 3 (b), Fig. 3 (c), Fig. 3 (d) SEM that the gold nanorods prepared after the prepared gold nano seed liquor of 3,5,15,50 μ L are added in embodiment 2 is successively represented Figure.
Fig. 4 is the ultraviolet-visible absorption spectroscopy of 2 different-diameter gold nanorods of embodiment；A, b, c, d successively represent embodiment 2 The middle ultraviolet-visible absorption spectroscopy that the gold nanorods prepared after the prepared gold nano seed liquor of 3,5,15,50 μ L are added.
Fig. 5 is that the absorption of embodiment 3 peak position is repaired in the ultraviolet-visible absorption spectroscopy and embodiment 4 of the gold nanorods of 808nm The ultraviolet-visible absorption spectroscopy of gold nanorods after decorations polyethylene glycol.
The function line chart of the Left Stellate Ganglions of experimental group and control group in Fig. 6 embodiment 5；Wherein, Fig. 6 (A), figure 6 (B), Fig. 6 (C), Fig. 6 (D) successively represent the irradiation of injection gold nanorods, injection gold nanorods do not irradiate, do not inject gold nanorods Only irradiation and the function line chart for not injecting the Left Stellate Ganglions that gold nanorods do not irradiate.
Specific embodiment
Below with reference to embodiment is implemented, the present invention will be further described.
Embodiment 1
Regulate and control the length of gold nanorods using silver ion: as follows
1. the preparation of gold nano seed liquor: CTAB aqueous solution being housed by being added in chlorauric acid solution (50 μ L, 0.05M) In the vial of (10mL, 0.1M), the 0.01M NaBH for preparing 0.6mL ice water under magnetic agitation (1200rpm)4Solution is added Into the solution, continues to stir 2min until becoming brown color, be reused after seed solution is saved 2h at room temperature.
2. the growth of different length gold nanorods: CTAB aqueous solution is added in chlorauric acid solution (200 μ L, 0.05M) In (20mL, 0.1M), prepare 6 groups in proportion, respectively number 1,2,3,4,5,6, then once into this 6 groups of solution be added 40, 80, the silver nitrate solution (0.01M) of 120,160,200,240 μ L is uniformly mixed, then the L- Vitamin C of brand-new is added to 6 groups of solution Growth-promoting media is made in acid solution (160 μ L, 0.1M).After obtained solution is mixed, under 25-30 DEG C of stirring condition, grow molten Liquid color is become colorless by faint yellow.Then, 400 μ L hydrochloric acid (1.0M) are separately added into and carry out pH value adjustment.It is gently mixed in solution After conjunction, it is separately added into seed solution (24 μ L).After mixing, about 12h is then stood at room temperature.Centrifugation (9000rpm, Gold nanorods 25min) are washed, are then rinsed for several times with deionized water.Liquid is discarded supernatant, then precipitating is dispersed in deionized water In.Ultravioletvisible absorption corresponding to the gold nanorods SEM picture and Fig. 2 for the different length being illustrated in fig. 1 shown below can be obtained Spectrum.
Embodiment 2
The diameter of gold nanorods is controlled using the additive amount of gold nano seed liquor, the specific steps are as follows:
1. prepared by gold nano seed liquor: will be added in chlorauric acid solution (50 μ L, 0.05M) equipped with CTAB aqueous solution (10mL, In vial 0.1M), the 0.01M NaBH for preparing 0.6mL ice water under magnetic agitation (1200rpm)4It is added to the solution In, continue stir 2min until solution become brown color, reused after seed solution is saved 2h at room temperature.
2. the growth of different-diameter gold nanorods: by by chlorauric acid solution (200 μ L, 0.05M), silver nitrate solution (200 μ L, 0.01M) and after CTAB aqueous solution (20mL, 0.1M) mixes in a glass tube, the L-AA solution of brand-new is then added Growth-promoting media is made in (160 μ L, 0.1M).After obtained solution is mixed, under mild stirring condition, growth solution color is by light Yellow becomes colorless.It adds 400 μ L hydrochloric acid (1.0M) and carries out pH value adjustment, be separately added into 3,5,15,50 μ after being sufficiently mixed again The prepared gold nano seed liquor of L.About 12h is stood at room temperature.It is centrifuged (9000rpm, 25min) washing and for several times, discards supernatant liquid, Again in deionized water by precipitating dispersion.The gold nanorods SEM picture and figure of the different-diameter being illustrated in fig. 3 shown below can be obtained Ultraviolet-visible absorption spectroscopy corresponding to 4.
Embodiment 3
Accurately absorption peak is prepared in the gold nanorods of 808nm, the specific steps are as follows:
1. gold nano seed liquor prepare: by chlorauric acid solution (50 μ L, 0.05M) be added equipped with CTAB aqueous solution (10mL, In vial 0.1M), the 0.01M NaBH for preparing 0.6mL ice water under magnetic agitation (1200 turns)4It is added in the solution, Continue to stir 2min until becoming brown color, obtains gold nano seed liquor；Gold nano seed liquor is saved after 2h again at room temperature It uses.
2. the growth of different length gold nanorods: CTAB aqueous solution is added in chlorauric acid solution (200 μ L, 0.05M) In (20mL, 0.1M), the silver nitrate solution (0.01M) that 200 μ L are added is uniformly mixed, then the L- newly prepared is added into solution and resists Growth-promoting media is made in bad hematic acid solution (160 μ L, 0.1M).After obtained solution is mixed, under mild stirring condition, grow molten Liquid color is become colorless by faint yellow.Then, 400 μ LHCl (1.0M) are separately added into and carry out pH value adjustment.It is gently mixed in solution Afterwards, 30 μ L gold nano seed liquors are added.After mixing, about 12h is then stood at room temperature.It is centrifuged (9000rpm, 25min) Gold nanorods are washed, are then rinsed for several times with deionized water.Liquid is discarded supernatant, then precipitating is dispersed in 25mL deionized water. The absorption peak that is illustrated in fig. 5 shown below can be obtained in the gold nanorods ultraviolet-visible absorption spectroscopy of 808nm.
Embodiment 4
Gold nanorods are surface modified, the specific steps are as follows:
It takes 4mL to be centrifuged (9000rpm, 10min) gold nanorods obtained in embodiment 3, is dispersed in 4mL deionization again In water, then 50 μ LmPEG-SH (1mM) are added in ultrasonic disperse, half h of mechanical oscillation places 12h at room temperature, centrifugation (9000rpm, 10min), which is scattered in again in 4mL phosphate buffered saline solution, can be obtained modification shown in following Fig. 5 red curve The ultraviolet-visible absorption spectroscopy of gold nanorods afterwards.
Embodiment 5
1. 24 adult domesticated dogs (18-24kg) are randomly divided into four groups, with 3% Nembutal vein anesthetic (30mg/ Kg) and three groups of control groups are arranged, respectively in anesthesia maintenance (2mL/h), progress open chest surgery, exposure Left Stellate Ganglions (LSG) It is not inject gold nanorods not irradiate, inject 100 μ L gold nanorods (concentration be 80 μ g/mL) and do not irradiate and do not inject gold nanorods Only irradiate.One group of experimental group, 100 μ L gold nanorods of injection (irradiate for 80 μ g/mL) and with the near-infrared laser of 808nm by concentration Neuromere.
2.LSG functional examination: it is inserted into the acupuncture needle of a diameter 0.1mm in LSG, one end of acupuncture needle is connected to Grass- S88 (Astro-Med, West Warwick, Rhode Island, USA) nerve stimulation instrument, granting frequency are 20Hz, pulsewidth The stimulation of 0.1ms.Pass sequentially through four-stage voltage (0-4V, 4-8V, 8-12V, 12-16V).Respectively before laxative and laxative light According to rear measurement different voltages intensity stimulate LSG caused by maximum heart rate change rate, and using stimulation voltage intensity as abscissa, with most Big change rate of heartbeat is that ordinate draws out voltage-heart rate response curve.Voltage-heart rate response curve reflects LSG function, also can Reflect the functional status of cardiac sympathetic nerve system.As shown in fig. 6, injection gold nanorods near-infrared irradiates rear left pleural ganglion function It can obviously be suppressed, control group does not find obvious inhibitory effect.
Two kinds of implementation methods of the invention above described embodiment only expresses, the description thereof is more specific and detailed.Not To limit the present invention, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be wrapped Containing within protection scope of the present invention.

Claims (3)

1. a kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation, which is characterized in that make by the following method It is standby to obtain:
(1) at 25-30 DEG C, the chlorauric acid solution that concentration is 0.05M is added in the CTAB aqueous solution that concentration is 0.1M, with The speed of 1200rpm stirs, and the concentration that ice water is prepared is the NaBH of 0.01M4Solution is added in above-mentioned solution, continues to stir 2min is until solution becomes brown color to get gold nano seed liquor is arrived；It is standby that gold nano seed liquor is saved to 2h at 25-30 DEG C With；Wherein, chlorauric acid solution, CTAB aqueous solution, NaBH4The volume ratio of solution is 1:200:12；
(2) at 25-30 DEG C, by concentration be 0.05M chlorauric acid solution be added concentration be 0.1M CTAB aqueous solution in, then plus Enter the silver nitrate solution that concentration is 0.01M, be uniformly mixed, then the L- that the concentration newly prepared is 0.1M is added into mixed solution and resists Bad hematic acid solution mixes, growth solution is made；It is stirred under the conditions of 25-30 DEG C, growth solution becomes nothing from faint yellow Color；Then salt acid for adjusting pH value is added to 2；Then 30 μ L gold nano seed liquors are added, 12h is stored at room temperature after mixing, is centrifuged, washes Wash, be absorbed peak 808nm gold nanorods；Wherein, chlorauric acid solution, CTAB aqueous solution, silver nitrate solution, L- Vitamin C Acid solution, gold nano seed liquor volume ratio be 20:2000:20:16:3；
(3) modify gold nanorods: the gold nanorods ultrasonic disperse that step (2) is obtained in deionized water, is added with sulfydryl Polyethylene glycol, mechanical oscillation 0.5h, is placed at room temperature for 12h, and the gold nanorods of surface modification sulfydryl can be obtained；
(4) gold nanorods for the surface modification sulfydryl that step (3) obtains are dispersed in phosphate buffered saline solution to get to being based on The Left Stellate Ganglions inhibitor of near-infrared laser irradiation.
2. the Left Stellate Ganglions inhibitor according to claim 1 based on near-infrared laser irradiation, it is characterised in that: The concentration that step (1) obtains Au in gold nano seed liquor is 2.5 × 10-6M。
3. the Left Stellate Ganglions inhibitor according to claim 1 based on near-infrared laser irradiation, it is characterised in that: The concentration of the gold nanorods of surface modification sulfydryl is 80 μ g/mL in step (4).
CN201810213285.5A 2018-03-15 2018-03-15 A kind of Left Stellate Ganglions inhibitor based on near-infrared laser irradiation Pending CN110269936A (en)

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Citations (2)

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Publication number Priority date Publication date Assignee Title
CN105170993A (en) * 2015-09-15 2015-12-23 中国人民解放军第二军医大学 Preparation method of gold nanorod modified by polyethylene glycol and application of gold nanorod modified by polyethylene glycol to restraining new vessel generation
CN205360244U (en) * 2015-12-22 2016-07-06 陕西省中医医院 Stellate neuromere stimulation instrument

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
CN105170993A (en) * 2015-09-15 2015-12-23 中国人民解放军第二军医大学 Preparation method of gold nanorod modified by polyethylene glycol and application of gold nanorod modified by polyethylene glycol to restraining new vessel generation
CN205360244U (en) * 2015-12-22 2016-07-06 陕西省中医医院 Stellate neuromere stimulation instrument

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叶天宇: "金纳米颗粒的可控制备及其光学性能研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 *
李志斌等: "星状神经节阻滞在心脏病治疗中的作用与意义", 《实用疼痛学杂志》 *
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