CN114617865A - Application of acetyl L-carnitine in preparing medicine for preventing or treating venous outflow obstruction diseases - Google Patents
Application of acetyl L-carnitine in preparing medicine for preventing or treating venous outflow obstruction diseases Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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Abstract
The invention discloses an application of acetyl L-carnitine in preparing a medicine for preventing or treating venous outflow disturbance diseases, and relates to the technical field of biomedicine. The invention firstly proposes that the acetyl L-carnitine not only can judge whether the venous outflow obstruction diseases occur and the morbidity degree, but also can be used as a medicine for relieving the venous outflow obstruction diseases, compared with the imaging examination, the content detection of the acetyl L-carnitine is quicker, easier to operate and strong in applicability, provides a way for the diagnosis, treatment and prognosis evaluation of the venous outflow obstruction diseases, and is beneficial to the development and application of further medicinal preparations and health-care foods.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of acetyl-L-carnitine in preparation of a medicine for preventing or treating venous outflow disturbance diseases.
Background
Cerebral venous drainage systems include the cerebral veins, the venous sinuses, and the structures of the neck veins responsible for cerebral venous drainage, abnormalities of which can lead to cerebral venous outflow disorders. There is increasing evidence that structural abnormalities in the cerebral venous system or disorders of cerebral venous outflow may lead to a variety of symptoms of impaired neurological function, such as headache/dizziness, tinnitus/tinnitus, blurred vision/visual field impairment/diplopia, sleep disorders, anxious depression, etc., and play an important role in the onset and progression of a variety of degenerative neurological diseases, such as parkinson's disease and various dementias including alzheimer's disease.
Cerebral venous outflow disorders can lead to a wide range of neuropathological impairments including blood brain barrier disruption, neurodegenerative changes, veno-derived cerebral microhemorrhage, abnormal cerebrospinal fluid production, impaired function of the lymphatic system, and disturbances in cerebral hemodynamics. Among them, transverse sinus-sigmoid sinus-internal jugular vein stenosis, chronic thrombosis, and internal jugular vein reflux caused by jugular vein valve lesion are common lesion types of cerebral vein outflow disorder, and they are also important reasons of the increase of cerebral vein pressure. In patients with mild cognitive impairment and Alzheimer's Disease (AD), internal jugular vein reflux reversibly transmits increased venous pressure into the cranium, thereby promoting the deposition of type I and type III collagen around cerebral and venular veins, ultimately resulting in thickening of venules and capillary basement membranes, accelerating the pathological progression of cognitive impairment. Keith et al also found that there was a significant increase in perivenous collagen in the brain tissue of AD patients, and it was a new finding in the neural field in recent years that cerebral venous outflow disorders could accelerate the progression of AD in view of the pathological remodeling of the vein wall in both cerebral venous outflow disorders and the pathological processes of AD.
With the development of aging of the population, cognitive impairment becomes a major health hazard for the elderly population. Lesions in the structure and function of cerebral blood vessels are the second most common cause of cognitive impairment. The previous research mostly focuses on cognitive impairment mediated by abnormal cerebral arterial system, and neglects the role of cerebral venous system diseases in cognitive impairment. Subject group preliminary studies found that 38% of patients with cerebral venous outflow disorder had symptoms of "memory loss", and Fulop et al also showed that cerebral venous outflow disorder is a potential cause of cognitive impairment. Therefore, the cerebral venous reflux disorder is a new target for preventing and treating the cognitive disorder diseases and drug development, and a new means for preventing and treating the cerebral venous reflux disorder is developed aiming at the pathological action of mediating cognitive impairment of the cerebral venous outflow disorder, thereby having important scientific significance and clinical value for preventing and treating the cognitive disorder diseases.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide application of acetyl-L-carnitine in preparing a medicament for preventing or treating venous outflow disturbance diseases.
The invention is realized by the following steps:
in a first aspect, the embodiments of the present invention provide the use of acetyl-l-carnitine for the preparation of a medicament for the prevention or treatment of disorders of venous outflow.
In a second aspect, the embodiments of the present invention provide the use of a composition comprising acetyl-l-carnitine in the preparation of a medicament for preventing or ameliorating venous outflow disorders.
In a third aspect, the embodiments of the present invention provide an application of acetyl l-carnitine and/or an agent for promoting synthesis of acetyl l-carnitine in the preparation of a health product for preventing or improving venous outflow disturbance diseases.
In a fourth aspect, the embodiments of the present invention provide an application of a reagent for detecting the content of acetyl-l-carnitine in a sample in the preparation of a kit for diagnosing or assisting in diagnosing venous outflow disturbance diseases.
The invention has the following beneficial effects:
the invention firstly provides that acetyl L-carnitine (ALCAR) can not only judge whether venous outflow disturbance diseases occur and the morbidity degree, but also be used as a medicine for relieving the venous outflow disturbance diseases, and compared with imaging examination, ALCAR content detection is faster, easier to operate and strong in applicability, provides a way for diagnosis, treatment and prognosis evaluation of the venous outflow disturbance diseases, and is beneficial to development and application of further medicinal preparations and health-care foods.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a schematic view of the operation of the rat cerebral venous outflow disorder model in example 1; wherein A is a rat model with cerebral vein outflow disorder, namely, the posterior vena cava and the internal jugular vein are ligated at the same time (shown by red opposite arrows); the B is a retroglenoid vein which is a continuation of a transverse extracranial sinus and mainly drains venous blood of an upper sagittal sinus and a straight sinus, is anastomosed with a superficial temporal vein and then is merged into a posterior facial vein and is merged with a anterior facial vein to form an external jugular vein, and finally flows out into the right atrium through the external jugular vein; c is a graph of the posterior glenoid vein separation exposure process;
FIG. 2 is a comparison of the vascular structure and function of the animals in the sham-operated group and the cerebral venous outflow disorder model group in example 1; wherein A is the result of two groups of animal intracranial vein imaging detection; b is the blood brain barrier destruction degree of two groups of animals-EB leakage condition; c is the blood brain barrier destruction degree of the two groups of animals, namely NaF leakage condition; d is the change ratio of the intracranial pressure of the two groups of animals;
FIG. 3 is the content of ALCAR in the hippocampus of the rat brain, cortical tissue and cerebrospinal fluid of example 1; wherein A is the content of ALCAR of hippocampal tissue, B is the content of ALCAR of cortical tissue, and C is the content of ALCAR of cerebrospinal fluid;
FIG. 4 is a graph showing the behavior of rats in exercise, cognition, etc. after feeding ALCAR (100mg/kg/day) in example 2; wherein, A-B are open field experiment results, C is Y-maze experiment results, D-E are rotating rod fatigue experiment results, and F is new object identification experiment results;
FIG. 5 is a graph showing the content of ALCAR in the hippocampus of the rat brain, cortical tissue, and peripheral blood and cerebrospinal fluid after feeding ALCAR (100mg/kg/day) in example 2;
FIG. 6 is a graph of the amount of ALCAR in the cerebrospinal fluid of the human in example 3.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Acetyl L-carnitine (ALCAR) is an endogenous molecule, is a dipeptide formed by the metabolism of lysine and methionine and having a molecular weight of 103Da, is expressed in various histiocytes such as brain, neurons and the like, and plays a main role in energy metabolism. As a precursor substance of the beta-oxidation of mitochondrial fatty acid, the ALCAR is transported into mitochondria through a carnitine shuttle mechanism, thereby promoting the lipid metabolism process of the organism. Meanwhile, ALCAR is also a regulatory neurotrophic factor, and the most important characteristic of the ALCAR is that the ALCAR can penetrate through a blood brain barrier so as to play a role in neuroprotection. It has good tolerance and little side effect.
ALCAR has a wide range of pharmacological effects, with neuroprotective and neurotrophic effects, regulating neurotransmitter production and activity, regulating neuronal function, preventing free radicals, enhancing cellular antioxidant capacity and repair, restoring and stabilizing mitochondrial activity, all with minimal side effects if dosed correctly. The ALCAR deficiency or insufficiency is manifested by symptoms of depression, cognitive impairment, aging and the like, and is mostly applied to the treatment of depression clinically. The ALCAR protects the brain from excitotoxics, oxidants, and apoptosis, thereby improving brain metabolic function and reducing oxidative stress and neurodegenerative disease.
The invention firstly proposes that the ALCAR not only can judge whether the venous outflow obstruction diseases occur or not and the disease degree, but also can be used as a medicine for relieving the venous outflow obstruction diseases. Therefore, the method can be further used for development and application of pharmaceutical preparations or health-care foods.
"treating" or "treatment" as used herein may refer to curing or reversing a disorder.
Specifically, the embodiment of the invention provides application of acetyl-L-carnitine in preparing a medicament for treating or improving venous outflow disturbance diseases.
Compared with other existing medicines, the acetyl-L-carnitine has the efficacy of treating or improving venous outflow disturbance diseases, and meanwhile, has extremely small side effect, and is beneficial to recovery and treatment of patients.
Preferably, the venous outflow disorder comprises at least one of a cerebral venous outflow disorder and an internal jugular venous outflow disorder.
Preferably, the venous outflow disorder is caused by at least one of a venous sinus thrombus and a venous sinus stenosis. When the venous outflow disorder is a cerebral venous outflow disorder, the cerebral venous outflow disorder is caused by at least one of cerebral venous sinus thrombosis, cerebral venous sinus stenosis, and jugular vein stenosis, i.e., the internal jugular vein disorder also causes the cerebral venous outflow disorder to cause a cerebral venous outflow disorder disease.
In a preferred embodiment, the obstructive disease of venous outflow comprises clinical symptoms, pathological lesions, or related diseases caused by the disorder of venous outflow.
In a preferred embodiment, the clinical symptoms include: headache, dizziness, tinnitus, blurred vision, visual field impairment, diplopia, sleep disorders, anxiety depression, and memory impairment (cognitive impairment).
In preferred embodiments, the associated disease comprises at least one of vascular, inflammatory, thrombotic, and degenerative diseases. Preferably, the degenerative disease comprises Alzheimer's Disease (AD).
In a preferred embodiment, the pathological lesions include: at least one of blood brain barrier disruption, neurodegenerative changes, veno-derived cerebral microhemorrhage, abnormal cerebrospinal fluid production, impaired function of the lymphatic system, and cerebral hemodynamic disorders, which pathological damage may be caused by a cerebral venous outflow disorder.
In a preferred embodiment, the number of portions of the medicament comprises one or more portions, each portion corresponding to a dose administered daily by the subject; when the subject to which the drug is administered is a rat, the dose of acetyl-L-carnitine contained in each drug is 50 to 150mg/kg, that is, the ALCAR is administered at a dose of 50 to 150mg/kg/day, and specifically, may be 50mg/kg/day, 60mg/kg/day, 70mg/kg/day, 80mg/kg/day, 90mg/kg/day, 100mg/kg/day, 110mg/kg/day, 120mg/kg/day, 130mg/kg/day, 140mg/kg/day, or 150 mg/kg.
In alternative embodiments, the type of the drug may be solid, liquid or gas, and is not particularly limited and may be prepared according to actual needs.
The embodiment of the invention provides application of a composition in preparing a medicament for preventing or treating venous outflow obstruction diseases, wherein the composition comprises acetyl L-carnitine.
Optionally, the composition further comprises other drugs applied to preventing or treating venous outflow obstruction diseases.
The treatment may refer to either a cure or a partial remission of clinical or pathological lesions.
It is understood that the specific definitions of the venous outflow obstruction diseases in this embodiment and the following embodiments are the same as those in the corresponding embodiments, and are not repeated herein.
The embodiment of the invention provides application of acetyl-L-carnitine and/or a reagent for promoting synthesis of acetyl-L-carnitine in preparation of health-care products for preventing or improving venous outflow disturbance diseases.
In addition, the embodiment of the invention provides application of a reagent for detecting the content of acetyl-L-carnitine in a sample in preparing a kit for diagnosing or assisting in diagnosing venous outflow disturbance diseases.
In an alternative embodiment, the method for detecting the content of acetyl-L-carnitine can be selected from the existing known detection methods, such as high performance liquid chromatography tandem mass spectrometry detection.
In a preferred embodiment, when the venous outflow disorder is a cerebral venous outflow disorder, the sample is a brain tissue sample or a cerebrospinal fluid sample of the animal. Specifically, the brain tissue includes at least one of hippocampal tissue and cortical tissue.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
1. Establishing a cerebral venous outflow obstruction animal (rodent) model;
adult (6-8 weeks old) female/male SD rats were selected and divided into two groups:
(1) sham control group (Sham group);
(2) an animal model which accords with the pathogenesis characteristics of human cerebral venous outflow disorder is designed according to the anatomical characteristics of head and neck veins of rodents, namely a postglenoid vein and internal jugular vein simultaneous ligation surgical scheme (JVL group), and the specific process is as follows: rats were anesthetized with isoflurane at 4% and the isoflurane concentration was maintained between 1.5% and 2% during surgery. Each rat was placed on a heat-insulating pad, and the neck and pre-auricular hair were removed with a shaver. Under the operating microscope, the field of view and focus of the microscope are adjusted, and conventional disinfection is performed by first making a longitudinal skin incision at the midline of the neck. Subcutaneous tissue and salivary glands were blunt-separated with vascular forceps, the dorsolateral side of the salivary glands was separated and the internal jugular veins (upper internal carotid artery, paravagus nerve) in the carotid sheaths on the left and right sides were sequentially separated and exposed, and the internal jugular veins were ligated with 8-0 non-absorbable surgical suture. The wound is sutured conventionally, roxithromycin antibiotic ointment is smeared at the wound, then, the skin of the ear and the area between the ear and the eye of the rat is disinfected conventionally, an oblique incision of about 1.5cm is made at the position 5mm near the front of the ear, the posterior facial vein, the superficial temporal vein and the posterior glenoid vein are carefully separated (as shown in figure 1), the posterior glenoid vein is ligated by using 8-0 non-absorptive surgical suture, the anesthesia is stopped, the wound is sutured conventionally, and the roxithromycin antibiotic ointment is smeared at the wound, and is bred conventionally 1 time per day for 5 consecutive days.
The comparison of the vascular structures and functions of the animals in the cerebral venous outflow obstruction model group and the animals in the sham operation control group established in the embodiment refers to fig. 2, in fig. 2, a shows that the expansion of the intracranial venous sinuses of the animals in the model group is more obvious, B-C shows that the blood brain barrier damage degree of the model group is obviously changed compared with the sham operation control group, and D shows that the change proportion of the intracranial pressure of the model group is obviously increased compared with the intracranial pressure of the sham operation control group. Through contrast tests, the model group animals show obvious functional/structural abnormality in the aspects of behavioral performance, blood brain barrier integrity and intracranial vascular morphological change, and meet the requirement of basic research on cerebral venous outflow disorder.
2. Non-targeted metabolomics screening for differential metabolites (see table 1).
TABLE 1 information on ALCAR differential metabolites
3. And (4) detecting the content of ALCAR in the brain tissue and the cerebrospinal fluid of the rat.
(1) Selecting 6 rats respectively in the JVL group 1 month after operation and the corresponding sham operation control group, anesthetizing with 4% chloral hydrate, collecting 0.2ml cerebrospinal fluid, perfusing with physiological saline, and removing blood. Taking out brain tissue quickly, and separating the sub-structures such as hippocampus, cortex and the like;
(2) the samples were processed as follows:
brain tissue (hippocampus and cortical tissue): washing brain tissue with precooled PBS (0.01M, pH7.4), removing residual blood, weighing, shearing, grinding (a system is configured according to the mass-volume ratio of 1: 9 of the tissue: PBS, namely 9ml of PBS buffer solution is added into 1g of tissue, and a certain amount of proteinase inhibitor PK is added), carrying out ultrasonic disruption on homogenate, centrifuging for 10min at 4 ℃ and 5000g, and taking supernatant for detection;
cerebrospinal fluid: centrifuging at 4 deg.C and 1000g for 20min, and collecting supernatant for detection;
(3) the steps were performed sequentially according to the instructions provided by the ALCAR detection kit (CCO400Ge-96T) from the company Cloud-clone Corp, and the RLU values were finally read on a chemiluminescence apparatus and concentration calculations were performed (FIG. 3).
As shown in FIG. 3A, the content of ALCAR in rat hippocampal tissue was significantly reduced in JVL group compared to Sham group. As shown in FIG. 3B, the content of ALCAR in rat cortical tissue was significantly reduced in the JVL group compared to that in the Sham group. As can be seen from C in FIG. 3, the ALCAR content in cerebrospinal fluid of rats in JVL group was significantly reduced compared to that in Sham group.
Example 2
Rat ALCAR feeding and behavioral testing.
Rats were randomly divided into four groups (n ═ 6 per group): the control group (Sham), the surgical group (JVL), the control + ALCAR group (Sham + ALCAR), the surgical + ALCAR group (JVL + ALCAR), and the four groups of rats were subjected to the same anesthesia and analgesia protocol.
(i) Sham group rats were subjected to a Sham surgery, and JVL group rats were subjected to a cerebral venous outflow disorder model (same as example 1). These rats were fed freely after surgery;
(ii) Sham + ALCAR group rats were subjected to pseudo-surgery, and JVL + ALCAR group rats were subjected to cerebral venous outflow disorder model construction. Adding ALCAR to the daily drinking water of the rat at a concentration of 100mg/kg/day after surgery, and allowing the rat to feed freely;
when the subject of the administration of the formulation is rat, the ALCAR is administered at a dose of 100 mg/kg/day.
After 1 month of feeding by ALCAR, the rats in all groups are subjected to behavioural test experiments such as pole-turning fatigue, open field, Y maze and new object identification, and the test results are shown in figure 4.
As shown in FIG. 4, the results of the open field experiment at A, B show that there is no significant difference in the total course and the central residence time between the rats in Sham and JVL groups, indicating that the cerebral venous outflow disorder has no effect on the motor ability of the rats. The Y-maze experiment result of C shows that the spontaneous alternation response proportion of the rats in the JVL group is obviously reduced compared with that in the Sham group, and the rats recover to be normal after being fed with ALCAR, which shows that ALCAR can improve/effectively relieve the memory/cognitive disorder of the rats in the JVL group. D. The results of the rod-rotating fatigue test of E show that the dropping time and the dropping speed of the rats in the Sham group and the JVL group have no obvious difference, which indicates that the cerebral venous outflow obstruction disease has no influence on the motor capacity of the rats. Compared with the Sham group, the new body recognition index of the rats in the JVL group is obviously reduced, and the rats recover to be normal after feeding ALCAR, which shows that ALCAR can improve/effectively relieve the memory/cognitive disorder of the rats in the JVL group.
The content of ALCAR in hippocampus of brain, cortical tissue, and peripheral blood and cerebrospinal fluid of all groups of rats is shown in fig. 5. As shown in FIG. 5A, the content of ALCAR in the hippocampal tissue of rats in the JVL group was significantly decreased compared to that in the Sham group, and increased and returned to a state similar to that in the Sham group (after feeding) when ALCAR was fed. As shown in FIG. 5B, the content of ALCAR in the rat cortical tissue was significantly decreased compared to that in the Sham group, and increased and returned to a state similar to that in the Sham group (after feeding) when ALCAR was fed. As can be seen from C in FIG. 5, the content of ALCAR in peripheral blood of rats in the Sham group and the JVL group was not significantly different, and was increased after feeding ALCAR. As shown in FIG. 5D, the ALCAR content in cerebrospinal fluid of the rats in JVL group was significantly decreased compared to that in Sham group, and increased and returned to the same level as that in Sham group (after feeding) when ALCAR was fed.
Example 3
And (4) detecting the ALCAR content in the human cerebrospinal fluid.
(1) Collecting cerebrospinal fluid of patients diagnosed with cerebral venous outflow disorder and non-central nervous system damage respectively, collecting with a common cerebrospinal fluid collecting tube according to conventional collecting operation, and storing in a refrigerator at-80 deg.C;
cerebrospinal fluid specimens of patients with non-central nervous system damage were retained using the following sampling criteria.
Inclusion criteria were:
patients with nervous system damage (such as hernia and fracture) except brain and spinal cord;
age and sex are not particularly limited.
Exclusion criteria:
presence of parkinson, senile dementia, epilepsy, any systemic malignancy;
venous sinus thrombosis, intracranial infection, vasculitis and other rheumatism immune diseases exist;
there are severe diabetes, liver and kidney dysfunction.
(2) The samples were processed as follows:
centrifuging at 4 deg.C for 20min at 1000g, and collecting supernatant.
(3) The steps were performed sequentially according to the instructions provided by the ALCAR detection kit (CCO400Ge-96T) from the company Cloud-clone Corp, and the RLU values were finally read on a chemiluminescence apparatus and concentration calculations were performed (FIG. 6).
As can be seen from the results, the ALCAR content in the patients was significantly reduced compared to the healthy controls. The ALCAR can be used as a detection marker for detecting diseases of the cerebral venous outflow obstacle, is verified in cerebrospinal fluid of clinical patients and healthy people, and has wide clinical application prospect.
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 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 (10)
1. Use of acetyl L-carnitine for the preparation of a medicament for the prevention or treatment of venous outflow disorders.
2. Use of acetyl-L-carnitine according to claim 1 in the preparation of a medicament for the prevention or treatment of disorders of venous outflow, wherein said disorders of venous outflow comprise disorders of venous outflow or the clinical symptoms, pathological lesions or related illnesses caused by disorders of venous outflow;
preferably, the venous outflow disorder comprises at least one of a cerebral venous outflow disorder and an internal jugular venous outflow disorder;
preferably, the venous outflow disorder is caused by at least one of a venous sinus thrombus and a venous sinus stenosis.
3. Use of acetyl-L-carnitine according to claim 2 in the preparation of a medicament for the prevention or treatment of disorders of venous outflow, characterized in that said clinical symptoms comprise: headache, dizziness, tinnitus, blurred vision, visual field impairment, diplopia, sleep disorder, anxiety, depression, and hypomnesia.
4. Use of acetyl-L-carnitine according to claim 2 in the preparation of a medicament for the prevention or treatment of disorders of venous outflow, wherein said associated disorder comprises at least one of vascular, thrombotic, inflammatory and degenerative disorders;
preferably, the degenerative disease comprises alzheimer's disease.
5. Use of acetyl-L-carnitine according to claim 2 in the preparation of a medicament for the prevention or treatment of disorders of venous outflow, characterized in that said pathological lesions comprise: at least one of blood brain barrier disruption, neurodegenerative changes, veno-derived cerebral microhemorrhage, abnormal cerebrospinal fluid production, impaired function of the lymphatic system, and cerebral hemodynamic disorders.
6. Use of acetyl L-carnitine according to any one of claims 1 to 4 in the preparation of a medicament for the prevention or treatment of disorders of venous outflow, characterized in that said fraction of medicament comprises one or more portions, each portion corresponding to the daily dose administered to a subject; when the administration object of the drug is rat, the dosage of acetyl-L-carnitine contained in each drug is 50-150 mg/kg.
7. Use of a composition for the manufacture of a medicament for the prevention or treatment of venous outflow disorders, wherein the composition comprises acetyl-l-carnitine;
preferably, the venous outflow disorder comprises at least one of a cerebral venous outflow disorder and an internal jugular venous outflow disorder.
8. The application of the acetyl L-carnitine and/or the reagent for promoting the synthesis of the acetyl L-carnitine in preparing the health care products for preventing or improving the venous outflow obstruction diseases;
preferably, the venous outflow disorder includes at least one of a cerebral venous outflow disorder and an internal jugular venous outflow disorder.
9. The application of the reagent for detecting the content of acetyl-L-carnitine in a sample in preparing a kit for diagnosing or assisting in diagnosing venous outflow disturbance diseases;
preferably, the venous outflow disorder comprises at least one of a cerebral venous outflow disorder and an internal jugular venous outflow disorder.
10. Use of the reagent for detecting the acetyl-L-carnitine content in a sample for the preparation of a kit for diagnosing or aiding in the diagnosis of a venous outflow disorder disease according to claim 9, wherein when the venous outflow disorder is a cerebral venous outflow disorder, said sample is a brain tissue sample or a cerebrospinal fluid sample of an animal.
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