CN113633893A - Application of plasma in preparation of medicine for improving or treating cerebral infarction and cerebral edema - Google Patents
Application of plasma in preparation of medicine for improving or treating cerebral infarction and cerebral edema Download PDFInfo
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- CN113633893A CN113633893A CN202110962884.9A CN202110962884A CN113633893A CN 113633893 A CN113633893 A CN 113633893A CN 202110962884 A CN202110962884 A CN 202110962884A CN 113633893 A CN113633893 A CN 113633893A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/44—Applying ionised fluids
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- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
- H05H1/00—Generating plasma; Handling plasma
- H05H1/24—Generating plasma
Abstract
The invention discloses application of plasma in preparing a medicament for improving or treating cerebral infarction and cerebral edema, and belongs to the technical field of medicines. The invention discovers the new application of the intermittent plasma in improving cerebral infarction and encephaledema for the first time, has the characteristics of uniformity, stability, safe contact and the like, and improves the treatment effect of diseases by giving plasma inhalation intervention when ischemic stroke occurs; can obviously reduce the cerebral infarction volume of a rat disease model with experimental ischemic stroke.
Description
Technical Field
The invention relates to application of plasma in preparing a medicament for improving or treating cerebral infarction and cerebral edema, belonging to the technical field of medicines.
Background
The stroke is a group of diseases which are mainly characterized by local nerve function deficiency due to cerebral blood circulation disorder, and is the first cause of death and disability of adults all over the world at present, while ischemic stroke is the most main type of stroke and accounts for 70% -80% of all stroke, and the main cause is cerebral tissue ischemic injury and nerve cell death caused by insufficient blood supply to the brain due to cerebrovascular diseases. In China, with the trend of aging of people and the change of life style of people, the incidence and mortality of ischemic stroke tend to rise year by year, and a heavy burden is brought to the society and families. Therefore, the development of preventive, therapeutic and health-care means for ischemic stroke-related diseases has become a hot spot in the field.
When ischemic stroke occurs, thrombolytic therapy of tissue plasminogen activator (rtPA) is performed at the first time, and the first choice of therapy is to restore cerebral blood flow supply through blocked blood vessels. Every 1 minute of prolonged ischemic injury to the brain, up to millions of brain cells undergo irreversible death, thereby affecting the patient's prognosis unpredictably. With the development of medical technology, the "time window" for ischemic stroke treatment can be extended to 3-4.5 hours, and in some cases even to 6 hours. However, due to the irreversibility of nerve cell death, many patients are treated with thrombolytic therapy, but the effect is still poor, and the patients are often accompanied with serious sequelae, such as aphasia, hemiplegia and the like, so that the life quality of the patients and family members is seriously affected, and a series of family social problems are caused. Therefore, when ischemic stroke occurs, certain measures can be taken to delay the erosion of the core area of cerebral ischemia to the peripheral normal brain tissue, so as to strive for time for thrombolytic therapy and have great significance for improving the final therapeutic effect.
In recent years, the application of low temperature plasma technology in the biomedical field has become an emerging research hotspot, and thus a new discipline, plasma medicine, has developed. Active particles (e.g. O) generated by plasma2-、NO-And N3-Etc.), charged particles, ultraviolet rays, etc., with gases, liquids, tissues, etc., and plasma is widely used in sterilization, dermatology, tumor therapy, oral medicine, wound healing, etc. The granted Chinese patent (ZL201511009739.X) discloses a method for protecting nerve cells, which discloses the protective effect of plasma on nerve cell damage in vitro, and it is noted that the patent discovers the pretreatment of H by plasma in vitro2O2Protection of SH-SY5Y nerve cells damaged by oxidative stress. The plasma nasal cavity inhalation interval and treatment conditions are optimized by accurately controlling the parameters of plasma generation and treatment, so that the plasma acting on a human body is always at physiological concentration, and intervention is given after ischemic stroke happens based on the physiological characteristics of the plasma, so that the progress of cerebral ischemic injury is delayed, and the final treatment effect is improved.
However, the development of plasma treatment devices in the past is limited to sterilization, tumor treatment, and skin disease treatment, which requires a large amount of active substances generated by plasma, and when the plasma is inhaled directly by human body, the dosage of plasma inevitably causes discomfort, and even aggravates the progress of the disease due to oxygen deficiency. How to develop a plasma device for treating nervous system diseases, which is simple and convenient to control and high in safety, by controlling the dosage of plasma is a problem to be solved urgently.
Disclosure of Invention
The invention aims to provide a new application of intermittent plasma inhalation in improving cerebral infarction and cerebral edema.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the application of the plasma in preparing medicines for improving or treating cerebral infarction and cerebral edema.
The plasma is one or more of low-temperature plasma, atmospheric pressure plasma and helium gas discharge plasma.
The plasma is a batch plasma.
The intermittent plasma refers to preparing a plurality of independent plasma releasing units, or intervening in an intermittent manner by continuously generating plasma, wherein each intermittent intervention of the plasma is regarded as an independent intervening unit, and 12-20 intervening units are needed in one complete process.
The reaction gas of the plasma is ultra-pure helium with the purity of 99.999 percent; the discharge driving voltage is 5.6 kilovolts, and the frequency is 5000 hertz sine alternating current. Each intervention unit comprises a plasma release time of 5-20 seconds and a pause time of 5-20 seconds.
The time interval between each plasma intervention unit is 1-30 seconds, preferably 5-20 seconds.
The plasma for treating the cerebral arterial thrombosis is generated by the plasma discharge device, a low-pressure environment is not needed, and the plasma can be directly generated under the atmospheric pressure condition. Can be used for improving the treatment effect of cerebral arterial thrombosis. After the nasal cavity inhales plasma, active particles in the plasma can reach a 'penumbra' around a brain injury area in the stroke through a circulatory system or a blood brain barrier behind the nasal cavity, so that the progress of the brain injury is delayed, and the treatment effect is improved. The invention provides a device for generating plasma discharge, which has the following advantages:
1. the plasma generator is simple to manufacture, easy to detach and replace electrodes, portable and movable.
2. The macroscopic temperature of the generated plasma beam is close to the normal temperature, and the normal cells or biological tissues are hardly damaged.
3. The plasma contains active substances which can generate beneficial effects on the nervous system, and the intervention is carried out in a mode of inhaling atmospheric pressure plasma through the nasal cavity, so that a new thought and means are provided for treating nervous system diseases.
In addition to the plasma discharge device described above, other devices having a generating and/or storing plasma discharge may be used.
Specifically, the invention discovers and proves the application of the plasma as the medicine for cerebral ischemia and cerebral infarction for the first time. The invention utilizes the intermittent plasma suction mode, not only ensures the effect of the plasma, but also controls the amount of the plasma, and does not cause oxidation/nitrification stress and damage generated by a large amount of plasma, thereby utilizing the physiological characteristics of the plasma and proving the treatment effect of the plasma on cerebral infarction and cerebral edema.
In early animal experiments, animals were given continuous plasma inhalation, but animals quickly asphyxiated to death. The invention creatively discovers that the intermittent administration mode avoids the asphyxia of animals and has an unexpected and definite treatment effect.
In animal cerebral apoplexy disease model experiment, inhale through 5 seconds plasma, the mode of 5 seconds of interval has fine effect, and the preferred intermittent type formula of inhaling of this patent intervenes.
In animal experiments to speculate the dose for human administration, the recommended reference intervals are: inhale 20 seconds, 10 seconds apart. For 5 minutes. It is particularly desirable to optimize the system according to the patient's condition, i.e. to ensure maximum inhalation without discomfort to the patient.
In addition, in some embodiments of the invention, a time control module is provided to synchronously control the power supply and the air supply of the plasma generator, and the plasma can be generated periodically by adjusting the time mode, so that the patient can inhale the plasma and the air alternately, and discomfort caused by long-time uninterrupted plasma inhalation is prevented.
Further, in some embodiments of the present invention, the plasma intensity and the active species concentration can be controlled by adjusting power supply parameters (such as voltage, frequency of voltage) and gas flow, different intervention intensities can be selected according to the disease degree of the nervous system, customized therapy is realized, and the application flexibility of the device is enhanced.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention. The objectives and other advantages of the invention may be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
It will be appreciated by those skilled in the art that the objects and advantages that can be achieved with the present invention are not limited to the specific details set forth above, and that these and other objects that can be achieved with the present invention will be more clearly understood from the detailed description that follows.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principles of the invention.
Fig. 1 is an overall configuration diagram of an intermittent plasma discharge apparatus according to embodiment 1 of the present invention.
Fig. 2 is a schematic structural diagram of a gas/circuit controller in embodiment 1 of the present invention.
Fig. 3 is a schematic diagram of a gas control module of the gas/circuit controller in embodiment 1 of the present invention.
Fig. 4 is a schematic structural diagram of a plasma generator in embodiment 1 of the present invention.
Fig. 5 is a schematic diagram of a control panel structure of the air/circuit controller in embodiment 1 of the present invention.
Fig. 6 is a cross-sectional view of an insulating fixing sleeve of a plasma generator according to embodiment 1 of the present invention.
Fig. 7 is an image example of a schematic operation and an actual operation of the plasma discharge model machine manufactured according to embodiment 1 of the present invention and the application of the device to a rat model of ischemic stroke disease.
FIG. 8 magnetic resonance Apparent Diffusion Coefficient (ADC) imaging of rats at various time points in example 3 of the present invention to detect cerebral infarct volume in rats.
Figure 9 is a statistical analysis of the infarct volume of the rats in figure 8 showing that plasma drying reduces infarct volume with respect to potency.
FIG. 10 shows the result of magnetic resonance T2 sequence imaging of rats in each group after 48 hours to detect the volume of cerebral edema of the rats.
FIG. 11 is a statistical analysis of the volume of cerebral edema in the rat of FIG. 10, showing that the plasma-dry prognosis can reduce the volume of cerebral edema.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the following embodiments and accompanying drawings. The exemplary embodiments and descriptions of the present invention are provided to explain the present invention, but not to limit the present invention.
It should be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and/or processing steps closely related to the scheme according to the present invention are shown in the drawings, and other details not so relevant to the present invention are omitted.
It should be emphasized that the term "comprises/comprising" when used herein, is taken to specify the presence of stated features, elements, steps or components, but does not preclude the presence or addition of one or more other features, elements, steps or components.
EXAMPLE 1 batch plasma discharge device
Fig. 1 shows a plasma device for treating a nervous system disease according to an embodiment of the present invention, the plasma device including: a gas cylinder 1, a gas/electric circuit controller 2 and a plasma generator 3, the gas cylinder 1 in the example of fig. 1 is a high purity gas tank in which helium gas or argon gas is stored. The gas cylinder 1 is connected with the gas/circuit controller 2 through a first gas pipe 41, and the gas/circuit controller 2 is connected with the plasma generator 3 through a second gas pipe 42, a high-voltage wire 43 and a ground wire 44. In the embodiment of the present invention, the term "high voltage line" refers to a line outputting a relatively high voltage with respect to a ground line, and is not used to limit a voltage applied to the high voltage line to a voltage of 10Kv or more. In embodiments of the invention, the voltage applied to the high voltage line is typically in the range of 0-10 kV.
As shown in fig. 2, the gas/electric circuit controller 2 includes a power supply control module 21, a gas control module 22, and an electric parameter module 23, and may further include a control panel (not shown in fig. 2). The power supply control module 21 may include a regulation power supply 211 and a time control module 212, wherein the regulation power supply 211 is connected with the plasma generator 3 via the high voltage line 43 and the ground line 44 to supply the plasma generator 3 with a voltage to be applied between its metal electrodes in order to generate a plasma jet with the discharge of the metal electrodes and the gas input into the plasma generator 3 by the gas control module. The voltage output by the regulation power supply 211 may be a constant voltage or a pulse voltage, the regulation power supply 211 may be provided with a voltage gear regulator and a frequency gear regulator, the voltage gear regulator is used for connecting the voltage value on the high-voltage line 43, the frequency gear regulator is used for adjusting the frequency of the output voltage, and the discharge intensity between the metal electrodes of the plasma generator 3 and the plasma jet length (discharge duration of the metal electrodes) may be controlled by adjusting the voltage and the frequency applied to the plasma generator. The time control module 212 may include a control motherboard and a logic circuit, and is configured to provide a synchronous control signal to the gas control module 22 and the plasma generator 3 via the logic circuit under the control of the control motherboard, that is, the output end of the time control module 212 is connected to both the gas control module 22 and the plasma generator 3, and is configured to control the power supply and the power off and the gas off of the plasma generator 3 to be synchronous. In the embodiment of the present invention, the plasma generator 3 may be operated in a set time mode, and the time mode (or discharge mode) may include an intermittent mode for intermittently supplying a high voltage to the plasma generator and a continuous mode for continuously supplying a high voltage to the plasma generator. In the embodiment of the invention, parameters such as time pattern, voltage, frequency, gas flow and total discharge time can be set or adjusted by using the control panel, the discharge intensity of the metal electrodes can be controlled by adjusting the voltage and frequency applied between the metal electrodes and the gas flow output by the gas control module, and the plasma generator 3 can be controlled to perform intermittent or continuous discharge at regular time by adjusting the time pattern and the discharge time.
As shown in fig. 3, the gas control module 22 includes a gas flow meter 221, a control chip 222, and a pneumatic solenoid valve 223. Specifically, as shown in fig. 3, one end of the gas flow meter 221 of the gas control module 22 is connected to the gas cylinder 1 through the first gas pipe 41, the other end is connected to the gas inlet of the pneumatic solenoid valve 223 for adjusting the gas flow, and the gas outlet of the pneumatic solenoid valve 223 is connected to the gas inlet 36 of the plasma generator 3 through the second gas pipe 42. The input end of the control chip 222 is connected to the time control module 212, the output end is connected to the pneumatic solenoid valve 223, and the air outlet of the pneumatic solenoid valve 223 is controlled to be opened or closed by identifying the synchronous control signal output by the time control module 212.
As shown in fig. 4, the plasma generator 3 may include an insulating housing 31, a first metal electrode 32, a second metal electrode 33, an insulating medium pipe 34, an insulating fixing sleeve 35, and a gas inlet 36. The first metal electrode 32, the second metal electrode 33, the insulating medium tube 34 and the insulating fixing sleeve 35 may be enclosed in an insulating case 31. The insulating housing 31 can be designed to be hand-held, so that the entire plasma generator 3 is small and portable and can be hand-held. In one embodiment, the insulating housing 31 of the plasma generator may be designed to be cylindrical, but the invention is not limited thereto, and may be other shapes that facilitate handling and/or facilitate packaging of other components therein. The gas bottle 1 is used for supplying gas to the plasma generator 3, the gas/circuit controller 2 is used for adjusting discharge parameters such as gas flow, voltage signal frequency and the like so as to control the discharge intensity of the plasma generator 3, and the power supply and the gas supply are controlled synchronously at regular time through the power supply control module 21 and the gas control module 22 so as to control the discharge time of the plasma generator 3. In addition, the electrical parameter module 23 connects the electric control module 21 and the gas control module 22, and the discharge parameter of the plasma generator 3 can be monitored by the electrical parameter module 23, so that the discharge state of the plasma generator 3 can be monitored.
As shown in fig. 4, the insulating housing 31 is further provided with a nozzle flush with the end of the insulating medium pipe 34, and the plasma jet is generated between the first metal electrode 32 and the second metal electrode 33 of the plasma generator, propagates to the end of the insulating medium pipe 34 and is ejected from the nozzle of the insulating housing 31.
In an embodiment of the present invention, the power supply control module 21 is connected to a high voltage line 43 and a ground line 44 penetrating through the insulating housing 31 of the plasma generator 3 via the electrical parameter module 23, and the high voltage line 43 and the ground line 44 are respectively connected to the first metal electrode 32 and the second metal electrode 33, so as to generate a high voltage for generating plasma between the first metal electrode 32 and the second metal electrode 33. The first metal electrode 32 is arranged in the insulating medium tube 34, the second metal electrode 33 covers the outer wall of the insulating medium tube 34, and the first metal electrode 32 and the second metal electrode 33 respectively penetrate out of the insulating shell 31 through the high-voltage wire 43 and the ground wire 44 to be connected with the power supply control module 21 and the electrical parameter module 23.
In some embodiments of the present invention, the electrical parameter module 23 is composed of meters related to voltage, output frequency of voltage, gas flow rate, etc., and is configured to monitor a discharge state of the plasma based on values of the meters, and help determine whether parameters of the plasma are abnormal or reach standards during intervention of the plasma, thereby maintaining safety and accuracy of treatment.
Specifically, as shown in fig. 5, the gas/electric circuit controller 2 is controlled by the control panel 24, and the control panel 24 is provided with a circuit main switch (main power switch) 241, a voltage adjusting knob 242, a frequency adjusting knob 243, a gas flow adjusting knob 244 and a time control main board 245. Time control motherboard 245 includes an electronic display 2451, a "time" selection button 2452, a "minute" selection button 2453, a "second" selection button 2454, and a time mode selection button 2455. The circuit master switch 241 is used for controlling the on-off of the whole circuit, the voltage adjusting knob 242, the frequency adjusting knob 243 and the gas flow adjusting knob 244 are respectively used for adjusting the voltage, the voltage frequency and the gas flow provided for the plasma generator 3, and the electronic display screen 2451 is used for displaying the selected time to indicate the total discharge time; the "hour" selection button 2452, the "minute" selection button 2453, and the "second" selection button 2454 are used to select the "hour", "minute", and "second" of time, and the time mode selection button 2455 is used to select the intermittent mode or the continuous mode.
Specifically, as shown in fig. 6, a set of through holes arranged in the axial direction may be provided in the insulating fixing sleeve 35 of the plasma generator 3, for example, the insulating fixing sleeve 35 may include a first through hole 351 and a second through hole 352, the first through hole 351 and the second through hole 352 may be coaxial but have different hole diameters, the first through hole 351 may have a hole diameter slightly larger than the diameter of the first metal electrode 32 for inserting and fixing the first metal electrode 32, and the second through hole 352 may have a hole diameter slightly larger than the diameter of the insulating medium pipe 34 for inserting and fixing the insulating medium pipe 34. In addition, a third through hole 353 may be further disposed on a side surface of the insulating fixing sleeve 35 along the vertical axial direction, and the third through hole 353 is adhered to the gas inlet 36 and is used for introducing gas into the insulating medium pipe 34. In an embodiment of the present invention, the air inlet 36 may be designed to be a tower shape to ensure good sealing performance when connecting with the air pipe, but the present invention is not limited thereto, and may be other shapes.
After the insulating medium tube 34 is inserted into the second through hole 352 and fixed, the first metal electrode 32 is inserted into the insulating medium tube 34 through the first through hole 351 and the second through hole 352, the second metal electrode 33 is tightly adhered to the outer wall of the insulating medium tube 34 at a distance from the first metal electrode 32, and plasma is generated between the first metal electrode 32 and the second metal electrode 33 and is ejected out of the nozzle of the insulating casing 31 from the tail end of the insulating medium tube 34. In some embodiments of the present invention, the first metal electrode 32 and the second metal electrode 33 may be a stainless steel needle and an aluminum foil ring, respectively, the insulating medium tube 34 may be a quartz glass tube, and the discharge mode used between the first metal electrode 32 and the second metal electrode 33 is a needle-ring dielectric barrier discharge. Here, the materials of the first metal electrode 32, the second metal electrode 33, and the insulating dielectric tube 34 are merely examples, and the present invention is not limited thereto, and the first metal electrode 32 and the second metal electrode 33 may be made of other metal electrode materials, and the insulating dielectric tube 34 may be made of other hard insulating media.
The plasma generator 3 of the present embodiment is used as follows: gas is introduced into the plasma generator 3 through the gas cylinder 1 and the gas control module 22, for example into the insulating fixing sleeve 35 of the plasma generator 3, the circuit master switch 241 is turned on by the control panel 24 of the gas/circuit controller 2, the voltage applied between the first metal electrode 32 and the second metal electrode 33, the frequency of the voltage output, the gas flow rate, and the like are adjusted, the plasma generation time is set by the "hour" selection button 2451, the "minute" selection button 2452, and the "second" selection button 2453, the time mode is set to the intermittent mode through the time mode button 2455, the time control module controls based on the time and the time mode set through the control panel, the plasma jet is intermittently generated at the nozzle of the insulating shell 31 of the plasma generator 3, and the nasal cavity is aligned to the plasma jet, so that the intermittent inhalation intervention can be performed on the patient. Under the control of the time control module 212, when the plasma generator 3 is powered on and supplied with air, the patient inhales the plasma jet, and when the plasma generator 3 is powered off and off, the patient inhales air, which is repeated repeatedly (for example, plasma inhales for 5 seconds, stops for 5 seconds, breathes air normally, and repeats repeatedly for 2 minutes). During the intervention, the electrical parameter module 23 monitors the plasma discharge state in real time. After the intervention is finished, the power supply control module 21 is automatically powered off, and the generation of the plasma beam current is stopped. In the invention, the macroscopic temperature of the generated plasma beam is close to the normal temperature, and the normal cells or biological tissues are hardly damaged.
The intermittent plasma discharge device provided by the embodiment of the invention has the advantages of small volume, simplicity in manufacturing, easiness in detaching and replacing the electrode, portability and mobility.
In addition, in some embodiments of the present invention, the atmospheric pressure plasma contains active substances that can beneficially affect the nervous system, and the intervention is performed in a manner that the atmospheric pressure plasma is inhaled through the nasal cavity, so that a new idea and means are provided for the treatment of nervous system diseases.
Furthermore, in some embodiments of the present invention, the time control module is arranged to synchronously control the power supply and the air supply of the plasma generator, and the time mode is adjusted to generate plasma periodically, so that the patient can inhale plasma and air alternately, thereby preventing discomfort caused by long-time uninterrupted plasma inhalation.
Furthermore, in some embodiments of the present invention, the plasma intensity and the active substance concentration are controlled by adjusting the power supply parameters and the gas flow rate, so that different intervention intensities can be selected according to the degree of cerebral ischemia, customized therapy is realized, and the flexibility of the device is enhanced.
EXAMPLE 2 plasma discharge device
A needle-ring dielectric barrier discharge structure is adopted, a quartz glass tube is used as a dielectric tube, a stainless steel needle with the inner diameter of 1mm, the outer diameter of 3mm and the curvature radius of about 0.05mm is used as a high-voltage electrode, a ground electrode is formed by winding an aluminum foil with the width of 2mm outside the quartz tube, and the distance from a needle point to the ground electrode and the distance from the ground electrode to a tube opening are 10 mm; the driving voltage is 5.6 kilovolts, the frequency is 5000 hertz, and the ultrapure helium (99.999 percent) discharges. The apparatus of this example was also used in the experiment of example 3.
Example 3 novel use of intermittent plasma inhalation for improving cerebral infarction and cerebral edema
First, experimental material
1. Plasma discharge device: the plasma discharge device manufactured in example 1 was applied to an intervention experiment of a rat cerebral ischemia model.
2. Experimental animals adult male SD rats weighing 200-. Rats were randomly assigned to sham-operated groups (operation only, no vessel embolization, for control), model groups, and plasma-aspirated groups, 6 per group, using a random number table. The experimental process follows the 3R principle to reduce the using number of animals and the pain of the animals.
Second, Experimental methods
1. Making a rat Middle Cerebral Artery Occlusion (MCAO) model:
the model is constructed by using a wire-embolism method to perform Middle Cerebral Artery Occlusion (MCAO) modeling of a rat, and the model is constructed by the specific operation of: 100mg/kg +10mg/kg ketamine + xylazine were injected intraperitoneally for anesthesia. After the successful anesthesia, performing a median incision on the neck of an SD rat, separating superficial muscles and fascia to find a common carotid artery, stripping a blood vessel at the bifurcation of the common carotid artery, dissociating partial common carotid artery, external carotid artery and internal carotid artery, ligating two ends of the external carotid artery by an artery clamp, cutting a small opening at the ligation middle position by an ophthalmic surgical scissors, preparing a 0.38mm silica gel-coated wire plug, penetrating the external carotid artery into the common carotid artery by holding the wire plug by an ophthalmic forceps, entering the common carotid artery, pushing the plug into the bifurcation of the internal carotid artery and the external carotid artery, and turning the plug into a proper position of the internal carotid artery to complete the MCAO model manufacture. The clamps are loosened and the incision is closed.
And carrying out MRI detection after 45min of model building to judge whether the model is successfully built.
2. And (3) administration intervention:
rats successfully modeled were selected and intervened by means of plasma nasal inhalation according to the method shown in figure 7.
Plasma intermittent inhalation intervention (figure 7) is given after 60 minutes of ischemic injury (timing is started after the wire plug is smoothly inserted into a blood vessel designated position), the specific intervention mode is that plasma inhalation is carried out for 5 seconds and stops for 5 seconds, the whole process is repeated, the whole process lasts for 2 minutes, and the magnetic resonance detection is carried out on the rat 15 minutes after the intervention, so as to evaluate the short-term effect of the intervention. And (3) after 90 minutes of modeling, anesthetizing the rat, pulling out the embolus, recovering blood flow supply, simulating a vascular recanalization process after stroke treatment, normally feeding the rat for 24 hours, observing the final effect, and respectively carrying out magnetic resonance and TTC (2, 3, 5-triphenyltetrazolium chloride) staining detection on the rat.
Third, experimental results
The results of fig. 8 and 9 show that the plasma treatment can reduce the cerebral ischemic volume in a short period of time, and can also significantly reduce the spread of cerebral ischemic injury areas; after the blood vessel is re-communicated for 24 hours, TTC staining and magnetic resonance images show that the volume of cerebral infarction is obviously reduced by plasma treatment, and the treatment effect can be obviously improved by the plasma treatment.
The results of fig. 10 and 11 show that brain edema was most severe after 48 hours of cerebral infarction, so that the rats of each group were kept for 48 hours and then subjected to MRI examination, and the results are shown in the following graph, which shows T2WI sequence magnetic resonance images of the rats of each group, and the light color region is the region of brain edema. The MCAO model group rats have obvious cerebral edema and obvious cerebral median line deviation. After plasma drying, the cerebral edema of the rat is obviously reduced.
The parameters in this model example are merely examples and are not intended to limit the invention, and parameters that are different for different patients and appropriate in severe cases are determined based on clinical trials or the like.
It is to be understood that the invention is not limited to the specific arrangements and instrumentality described above and shown in the drawings. A detailed description of known methods is omitted herein for the sake of brevity. In the above embodiments, several specific steps are described and shown as examples. However, the method processes of the present invention are not limited to the specific steps described and illustrated, and those skilled in the art can make various changes, modifications and additions or change the order between the steps after comprehending the spirit of the present invention.
It should be noted that the exemplary embodiments of the present invention describe some methods or systems based on a series of steps or devices. However, the present invention is not limited to the order of the above-described steps, that is, the steps may be performed in the order mentioned in the embodiments, may be performed in an order different from the order in the embodiments, or may be performed simultaneously.
Features that are described and/or illustrated with respect to one embodiment may be used in the same way or in a similar way in one or more other embodiments and/or in combination with or instead of the features of the other embodiments in the present invention.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes may be made to the embodiment of the present invention by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. The application of the plasma in preparing medicines for improving or treating cerebral infarction and cerebral edema.
2. Use according to claim 1, characterized in that: the plasma is one or more of low-temperature plasma, atmospheric pressure plasma and helium gas discharge plasma.
3. Use of a plasma according to claim 1 or 2, characterized in that: the plasma is a batch plasma.
4. Use according to claim 3, characterized in that: the intermittent plasma refers to preparing a plurality of independent plasma releasing units, or intervening in an intermittent manner by continuously generating plasma, wherein each intermittent intervention of the plasma is regarded as an independent intervening unit, and 12-20 intervening units are needed in one complete process.
5. Use according to claim 4, characterized in that: the reaction gas of the plasma is ultra-pure helium with the purity of 99.999 percent; the discharge driving voltage is 5.6 kilovolts, and the frequency is 5000 hertz sine alternating current. Each intervention unit comprises a plasma release time of 5-20 seconds and a pause time of 5-20 seconds.
6. Use according to claim 4, characterized in that: each plasma is applied to the cell with a time interval of 1-30 seconds between each plasma and the cell.
7. Use according to claim 6, characterized in that: each plasma is applied to the cell with a time interval of 5-20 seconds between each plasma and the cell.
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