The minimum lethal dose of scorpion venom measured by sequential method was 0.07mg/kg in rabbits and 0.5mg/kg in mice, and the LD50 of the decoction of scorpion body injected intravenously in mice was 6.148g/kg, and the LD50 of scorpion tail was 0.88g/kg. Scorpion venoms produced in different regions may vary greatly, and the LD50 of the scorpion venom produced in Liaoning was 10.3mg/kg for intraperitoneal injection into mice, and the LD50 of the venom produced in Henan and Shandong was 2.4mg/kg for intraperitoneal injection into mice. The LD50 of scorpion venom from Liaoning is 10.3 mg/kg for intraperitoneal injection in mice, the LD50 of scorpion venom from Henan and Shandong is 2.4 mg/kg for intraperitoneal injection in mice, the LD50 of scorpion venom from Hebei is 2.79 mg/kg for intraventricular injection in mice, and the maximal safe amount of antiepileptic peptide for intraventricular injection is 5.6 mg/kg in mice. ).

Toxic reactions are often characterized by respiratory toxic reactions and neurotoxic reactions. Symptoms can start within minutes after scorpion bite and usually reach the most severe level within 5h. The main manifestations are local burning pain, sensory hypersensitivity, redness, swelling and bruising; and pupil dilation, nystagmus, excessive salivation, dysphagia and agitation and other central nervous system and autonomic nervous system symptoms; occasionally, respiratory and cardiac failure, or even death. Victims of different high-risk scorpion stings around the world have similar symptoms such as massive release of hormonal levels of catecholamines, glucagon, cortisol, angiotensin II, insulin, and elevated blood glucose levels, and finally multifunctional organ failure and death. In anesthetized rabbits, intravenous injection of scorpion venom 0.5mg/kg caused an increase in arterial blood pressure, slowing of heart rate, arrhythmia, gradual slowing of respiratory rate, and ultimately death due to respiratory arrest. Scorpion venom can also affect cytochrome oxidase and metabolic acid oxidase system, causing delay or disappearance of fetal ossification center, resulting in fetal skeletal abnormality, with teratogenic effects. Scorpion venom has no mutagenic effect on human blood lymphocytes, but can produce obvious cytotoxic effects.

Research has shown that scorpion venom acts rapidly in the body, but has a short half-life, and the symptoms of acute systemic poisoning may improve after a few hours, with a delay of 1-2 days at most. Scorpion venom by intraperitoneal injection can quickly spread to the whole body (not through the blood-brain barrier), and scorpion venom gavage LD50 is hundreds of times the intraperitoneal injection LD50, gavage anticancer effective dose and the latter is comparable, because of the toxicity of proteins are not easy to pass through the gastrointestinal mucosa, coupled with the role of gastric acid, the general symptoms of poisoning is not obvious. Thus, the safety coefficient of scorpion venom as an antitumor drug for oral administration is larger. In the application process of scorpion venom anti-tumor, if the patient's upper gastrointestinal mucosa has defects or gastric acid secretion is less, the oral dose should be strictly controlled to prevent poisoning. Sodium channels

The toxins that act on the sodium channel target receptor binding site 4 are framed as alpha type only. They are mainly produced in scorpion species from North and South America. Of these, the CssII toxins are considered to be the signature modulators acting at this site. They generally consist of 60-66 amino acid residues, and a hydrophobic region located on one side of the molecule is thought to be potentially important in facilitating the interbinding process between the toxin and its target receptor binding site.

High-affinity binding of β-scorpion toxins to their target receptor site 4 shifts the activation phase voltage of the sodium channel in the direction of hyperpolarization, whereas it has little effect on the inactivation phase of the sodium channel. This class of toxins has two high-affinity equilibrium binding sites on the target receptor (Kd=0.1 nmol/L and 5 nmol/L), and their binding to their target receptor sites is unaffected by cell membrane potential and other toxins. However, different β-scorpionic toxins are able to compete with each other for binding. β-Scorpionic toxins are able to shift the activation threshold potential of sodium channels only if the channels are pre-depolarized and open, and their binding is dependent on the specific conformation of the receptor site. The Voltage-sensorTrap-ping model suggests that under a pre-depolarizing stimulus, which induces the opening of the sodium channel and the outward movement of the voltage receptor S4 fragment, β-scorpionic toxin can bind to the IIS3-S4 loop of the target receptor site, i.e., it interacts with the extracellular region of the IIS4 fragment, and stably captures the S4 fragment, keeping it in the activated position. Site-directed mutagenesis experiments confirmed that multiple extracellular loops of the sodium channel β-subunit are high-affinity binding sites for β-scorpion-like toxins, with the S1-S2 extracellular loops of homologous region II and the S3-S4 loops of the extracellular terminus of the S4 fragment being the most important. Residue Gly-845 in the IIS3-S4 loop and residue Pro-782 in IIS1-S2 are also among the high-affinity binding sites of β-scorpionotoxin, and Gly-845 is necessary for the alteration of voltage-dependent activation of β-scorpionotoxin toward hyperpolarization.

Two other classes of long-chain scorpion toxins, excitatory and inhibitory anti-insect toxins, are also categorized as β-like scorpion toxin subtypes. They are mostly produced in Eurasian scorpion species and have a mode of action similar to that of β-scorpion toxins: both affect the activation process of insect sodium channels; their binding to insect target receptors is not dependent on membrane potential; and their binding to insect neural specimens can be replaced by competition from β-scorpion toxins. Excitatory anti-insect toxins have only a single high-affinity, low binding capacity binding site with insect sodium channels; inhibitory anti-insect toxins have two unrelated target receptor binding sites on insect neuronal cell membranes: one is a high-affinity, low-binding capacity site, and the other is a low-affinity, high-binding capacity site, of which the high-affinity site is very close to the excitatory anti-insect toxin's binding site, but not identical. The high affinity site is very close to the binding site of excitotoxin, but not exactly the same. The molecular binding experiments suggest that the extramembrane regions of the structural domains I, III, and IV of the insect sodium channel may constitute a complex binding site for anti-insect toxins.

Potassium channels

Hyperkalemia or hyponatremia occurs in scorpion bites, and the large number of ion channel blockers contained in scorpion venom interferes with normal sodium-potassium homeostasis. Endothelial cells do not express voltage-gated calcium channels, but calcium homeostasis has a very important role in endothelial cell function. K+ channels expressed on the cell membrane are thought to regulate cell membrane potential as a means of influencing intracellular calcium levels.K+ channels are involved in neuronal regulation and electrocardiographic patterns, muscle contraction, neurotransmitter release, hormone secretion, regulation of cellular secretions, and lymphocyte activation. There are four main types of potassium channels on endothelial cell membranes: large conductance calcium-activated potassium channels (BKca), intermediate conductance-activated potassium channels, small conductance calcium-activated potassium channels, and voltage-gated potassium channels.

Introns

Different toxin genotypes have distinctly different intron sizes, showing a clear superfamily distribution, with most of the Na+ channel toxins having introns between 300-590 bp, longer introns, and three longer ones, while the K+ channel toxins and Cl- channel toxins have introns between 74-125 bp (with the exception of long-chain K+ channel toxins K+ channel toxins and Cl- channel toxins have introns between 74-125 bp (except for long chain K+ channel toxins), which are shorter; and some toxin genes contain no introns. These different types of toxin genes may have originated from the same proto-gene, and their introns have evolved in concert with the exons, while in some genes the introns have been excised during the evolutionary process. Most introns are inserted between bases 1 and 2 of an amino acid codon in the signal peptide, between 43-55 bp from the start of the gene (ATG). α Na+ channel toxins generally have introns inserted in the -4 position of the small nonpolar amino acid coding base, whereas β Na+ channel toxins generally have introns inserted in the -4 or -6 position of nonpolar or polar amino acid coding bases; K+ channel toxins and Cl- channel toxins are inserted in amino acids at positions -5-10.

Membrane toxins

Domestic and foreign scholars usually believe that the toxicity of scorpion venom is mainly through the influence of sodium and potassium ion channels on the cell membrane and play a role, but some people believe that the scorpion venom may be through the interaction with the membrane lipids-membrane proteins on the cell membrane to produce its physiological and pharmacological effects, so also called scorpion venom for "membrane toxin". Therefore, it is also called "membrane toxin". The most toxic BmK4 LD50=0.34Lg/g body weight, which is 40-100 times higher than that of the crude venom (LD500.34Lg/g body weight of the crude venom), and the molecular weights are 6600, 5000 and 8500, respectively, and the molecular weights of BmK4 LD50=0.34Lg/g body weight, which is 40-100 times higher than that of the crude venom (LD500.34Lg/g body weight of the crude venom). The molecular weights were 6600, 5000 and 8500; the isoelectric points were 8.7, 9.1 and 9.1, respectively.It was found that the purified Peak Ⅲ had an inhibitory effect similar to that of ouabain on the Na+-K+-ATPase of the human erythrocyte membranes, and the inhibitory rate could be up to 25%-40% at 10-6mg/mL.The three purified fractions also reduced the mobility of the human erythrocyte membranes, which indicated that the toxic effect of scorpion venom was related to its effect on the human erythrocyte membrane. The toxic effect of scorpion venom is related to its interaction with cell membrane. However, little research has been done in this area. For scorpion sting injuries, there were some relevant treatments in ancient Chinese books. Tao Yinju in the "Collection of Examinations and Formulas Volume 9" in the cloud: scorpions have male and female, the male stings pain stop in one place; female pain pulling a few places. If the male stings with well mud, it is easy to warm it up; if the female stings with mud under the trench of the house, it is easy to warm it up. Another cloud: once the pain of the sting was intolerable, all the treatment is not effective, some people make cold water to stain the fingers and hands, that is, no pain, the water is slightly warm again pain, that is, easy to cold water, the rest of the place can not be immersed in cold water, then the cloth top of the old, small warm is easy, are all tested. The treatment of scorpion venom is described in the Materia Medica Bibliografica Scale and Fish Insects Department as follows: If a person is stung by a scorpion, applying snail will relieve the stings. Early treatment is needed to save the patient's life. Therapeutic drugs usually include: prazosin, angiotensin-converting enzyme (ACE) inhibitors, insulin, and antitoxin serum.

Early gastric lavage with 1:5000 potassium permanganate solution is recommended, followed by internal administration of 20-30g of activated charcoal. 2000-3000mL of 5% dextrose saline can be placed on static drip to promote the excretion of scorpion toxin to achieve the water-electrolyte balance. For those who have systemic symptoms after poisoning, 10% calcium gluconate 10ml IV; 10% chloral hydrate retained enema; atropine 1-2mg intramuscular injection; cortisone 100ml IV, and also give antihistamines to prevent hypotension, pulmonary edema; also can be injected into the anti-scorpion venom serum, which can quickly alleviate the symptoms of poisoning. Traditional Chinese medicine treatment: 30g of honeysuckle, 9g of hemicranium, 15g each of Poria cocos and mung bean, 9g of licorice, decocted twice with water, combined together, and divided in the morning and evening, which can neutralize the toxicity or detoxify scorpion venom toxin. Research reports show that the combination of antiscorpionic venom serum and prazosin can greatly improve the speed of recovery of patients, and the antivenom scorpion-specific F (ab?) was able to relieve the clinical syndrome within 4 h after its use in critically ill pediatric patients.