CN112189625A - Rat lung injury model with different severity induced by intratracheal spraying of bleomycin with different doses - Google Patents
Rat lung injury model with different severity induced by intratracheal spraying of bleomycin with different doses Download PDFInfo
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- 108010006654 Bleomycin Proteins 0.000 title claims abstract description 43
- 229960001561 bleomycin Drugs 0.000 title claims abstract description 43
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 title claims abstract description 43
- 208000004852 Lung Injury Diseases 0.000 title claims abstract description 33
- 206010069363 Traumatic lung injury Diseases 0.000 title claims abstract description 33
- 231100000515 lung injury Toxicity 0.000 title claims abstract description 33
- 238000005507 spraying Methods 0.000 title claims abstract description 15
- 210000003437 trachea Anatomy 0.000 claims abstract description 19
- 238000011160 research Methods 0.000 claims abstract description 9
- 230000037396 body weight Effects 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- 230000029058 respiratory gaseous exchange Effects 0.000 claims abstract description 5
- 230000001678 irradiating effect Effects 0.000 claims abstract description 4
- 210000000214 mouth Anatomy 0.000 claims abstract description 4
- 241000700159 Rattus Species 0.000 claims description 54
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 206010035664 Pneumonia Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims description 2
- 238000002663 nebulization Methods 0.000 claims 6
- 229940079593 drug Drugs 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 241001465754 Metazoa Species 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 6
- 239000001569 carbon dioxide Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 208000031873 Animal Disease Models Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/20—Animals treated with compounds which are neither proteins nor nucleic acids
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
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- Life Sciences & Earth Sciences (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides rat lung injury models with different degrees of severity induced by intratracheal spraying of different doses of bleomycin. The method comprises the following steps: anaesthetizing the rat, and immediately fixing the rat on an inclined plane fixing table in a supine position after the rat reaches an anaesthetizing state so as to smoothly find an opening of a trachea through the oral cavity of the rat; irradiating the lower jaw of the neck of the rat by using a cold light source so as to obtain an adequate light source during the subsequent oral operation; pulling out the tongue of the rat, pressing the tongue root by the tongue depressor, and finding the opening of the trachea; an 'trachea inner atomizer' is used, a needle head of the atomizer is directly inserted into a trachea of a rat by 3-4 cm, the breathing rule of the rat is observed, bleomycin (10mg/kg-80mg/kg body weight) with different doses is rapidly sprayed into an airway at the moment of rat inspiration, and then the rat is kept on a slope retaining table for 5-30 s. The invention has the advantages of stability, controllable mortality and better consistency, can simulate rat lung injury models with different clinical severity degrees, and provides more reliable animal experimental materials for preclinical research of medicines.
Description
Technical Field
The invention relates to an animal disease model, in particular to a rat lung injury model with different severity induced by intratracheal spraying of bleomycin with different doses.
Background
A stable lung injury model with controllable severity and mortality and good consistency is an important carrier and basis for preclinical research of lung disease treatment drugs. The common rat lung injury model at present is that after the trachea is exposed by neck surgery, the trachea is punctured, bleomycin is instilled in the trachea, the dose is 5mg/kg, the death rate of the model is high, the molding rate is low, and the consistency of the model is poor. And the lung injury states of different clinical severity degrees cannot be stably and well simulated, so that the research on lung injury related researches in different disease courses is hindered.
Disclosure of Invention
The technical problem to be solved is as follows: the invention aims to provide a rat lung injury model with different degrees of severity induced by intratracheal spraying of bleomycin with different doses, which is stable, controllable in mortality rate, better in consistency and capable of simulating the rat lung injury model with different degrees of severity clinically and provides a more reliable experimental material for preclinical medical research.
The technical scheme is as follows: the method for establishing the rat lung injury model with different degrees of severity induced by intratracheal spraying of bleomycin with different doses comprises the following steps:
(1) after anesthetizing healthy rats, carrying out intratracheal spraying and administration of bleomycin according to the dose of 10mg/kg-80 mg/kg;
(2) and observing different severity degrees of the rat lung injury induced by the bleomycin with different doses after administration, and constructing the rat lung injury model.
Further, the dosage in the step (1) is 10mg/kg-80 mg/kg.
Further, the specific operation of the intratracheal spray administration in the step (1) is as follows:
1) anaesthetizing the rat, and immediately fixing the rat on an inclined plane fixing table in a supine position after the rat reaches an anaesthetizing state so as to smoothly find an opening of a trachea through the oral cavity of the rat;
2) irradiating the lower jaw of the neck of the rat by using a cold light source so as to obtain an adequate light source during the subsequent oral operation;
3) pulling out the tongue of the rat, pressing the tongue root by the tongue depressor, and finding the opening of the trachea;
4) the method comprises the steps of using an 'trachea inner atomizer', directly inserting an atomizer needle head into a rat trachea for 3-4 cm, observing the breathing rule of the rat, rapidly spraying bleomycin with different doses into an airway at the moment of rat inspiration, and then keeping the rat on an inclined plane retaining table for 5-30 s.
Further, the administration mode of the bleomycin is intratracheal spraying.
Furthermore, the dosage of the bleomycin in the model construction is 10mg/kg-80mg/kg of body weight, and the corresponding dose of the bleomycin is selected according to the severity of the required model.
The rat lung injury model with different degrees of severity induced by intratracheal spraying of different doses of bleomycin is applied to scientific research on lung injury diseases such as bronchitis, aseptic pneumonia, pulmonary fibrosis, acute lung injury, respiratory distress syndrome and the like.
Has the advantages that:
1. the model is an intratracheal bleomycin spray induced lung injury model under the noninvasive condition, the molding process is simpler and quicker, the complex operation of experiments is avoided, and the unnecessary influence on animals and experimental research is smaller.
2. The bleomycin is uniformly distributed in the lung of the model rat, so that the lung injury is uniform, and the stability and consistency of the model are better.
3. The model avoids the defects of high death rate and poor model consistency under the unintended condition. The severity of the lung injury of the model and the mortality of the model are closely related to the dosage of the model drug, and the severity of the lung injury of the model and the mortality of the model can be accurately controlled by adjusting the dosage of the model drug.
4. The lung injury rat disease models with different severity degrees provide more reliable, more diverse and more corresponding animal lung injury models for preclinical research of medicines.
Drawings
In the dose range of 10-80mg/kg of Bleomycin (BLM), the doses of 10mg/kg, 20mg/kg, 30mg/kg, 40mg/kg and 80mg/kg are taken as examples:
fig. 1 is a graph comparing tidal volumes at different doses of BLM.
Fig. 2 is a graph comparing respiratory rate at different doses of BLM.
FIG. 3 shows the partial pressure of arterial blood oxygen (PO) at different doses of BLM2) Compare the figures.
FIG. 4 is the oxygen Saturation (SO) at different doses of BLM2) Compare the figures.
FIG. 5 shows partial carbon dioxide Pressure (PCO) of arterial blood at different doses of BLM2) Compare the figures.
FIG. 6 shows the carbon dioxide saturation (tCO) for different doses of BLM2) Compare the figures.
FIG. 7 is a graph comparing the degree of fibrosis in lung tissue at different doses of BLM.
Detailed Description
Rats were divided into 6 groups of 6 rats (male and female halves) each, weighing 180-220 g, normal control groups at 10mg/kg, 20mg/kg, 30mg/kg, 40mg/kg, 80mg/kg doses, respectively.
1) Anaesthetizing the rat, and immediately fixing the rat on an inclined plane fixing table in a supine position after the rat reaches an anaesthetizing state so as to smoothly find an opening of a trachea through the oral cavity of the rat;
2) irradiating the lower jaw of the neck of the rat by using a cold light source so as to obtain an adequate light source during the subsequent oral operation;
3) pulling out the tongue of the rat, pressing the tongue root by the tongue depressor, and finding the opening of the trachea;
4) the method comprises the steps of using an 'trachea inner atomizer', directly inserting an atomizer needle head into a rat trachea for 4cm, observing the breathing rule of the rat, rapidly spraying the bleomycin with different doses into an airway as an experimental group at the moment of rat inspiration, spraying physiological saline on a blank control group, and keeping the rat on a slope retaining table for 20 s.
The tidal volume, respiratory rate, arterial blood oxygen partial Pressure (PO) were performed on 6 groups of rats2) And oxygen Saturation (SO)2) Arterial blood partial pressure of carbon dioxide (PCO)2) And carbon dioxide saturation (tCO)2) The degree of fibrosis of lung tissue, etc., and the results are shown in FIGS. 1 to 7.
As shown in fig. 1, after different doses of Bleomycin (BLM) were modeled, rat tidal volumes were gradually decreased as BLM dose increased; as shown in fig. 2, the breathing rate is stepped up as the BLM dose is increased; as shown in FIGS. 3 and 4, partial pressure of arterial oxygen (PO)2) And oxygen Saturation (SO)2) (ii) a gradual decrease with increasing BLM dose; arterial partial carbon dioxide Pressure (PCO) as shown in FIGS. 5 and 62) And carbon dioxide saturation (tCO)2) Escalation with increasing BLM dose; as shown in fig. 7, the degree of lung tissue fibrosis progressively worsened with increasing BLM dose; the number of alveoli decreases progressively with increasing BLM dose.
The lung injury diagnostic method is consistent with the respiratory parameters, blood gas and pathological changes of lung injury diseases with different clinical courses and different severity degrees, and can better reflect clinical characteristics.
In preclinical studies, models of varying severity can be selected for drug studies, depending on the needs of the experiment.
Claims (6)
1. Rat lung injury models of different severity induced by intratracheal spraying of different doses of bleomycin are characterized by comprising the following steps:
(1) after anesthetizing healthy rats, intratracheal spraying bleomycin according to the dose of 10mg/kg-80mg/kg body weight;
(2) and observing different severity degrees of the rat lung injury induced by the bleomycin with different doses after administration, and constructing the rat lung injury model.
2. The model of lung injury in rats of varying severity induced by intratracheal nebulization of varying doses of bleomycin according to claim 1, wherein the dose administered in step (1) is from 10 to 80mg/kg body weight.
3. The rat lung injury model of different severity induced by intratracheal nebulization of different dose of bleomycin according to claim 1, wherein the specific operation of intratracheal nebulization administration in step (1) is:
1) anaesthetizing the rat, and immediately fixing the rat on an inclined plane fixing table in a supine position after the rat reaches an anaesthetizing state so as to smoothly find an opening of a trachea through the oral cavity of the rat;
2) irradiating the lower jaw of the neck of the rat by using a cold light source so as to obtain an adequate light source during the subsequent oral operation;
3) pulling out the tongue of the rat, pressing the tongue root by the tongue depressor, and finding the opening of the trachea;
4) an 'trachea inner atomizer' is used, a needle head of the atomizer is directly inserted into a trachea of a rat by 3-4 cm, the breathing rule of the rat is observed, bleomycin (10mg/kg-80mg/kg body weight) with different doses is rapidly sprayed into an airway at the moment of rat inspiration, and then the rat is kept on a slope retaining table for 5-30 s.
4. The model of intratracheal (i.v.) nebulization of bleomycin-induced lung injury in rats of varying severity according to claim 3, wherein: the mode of administration of bleomycin is by intratracheal nebulization.
5. The model of intratracheal (i.v.) nebulization of bleomycin-induced lung injury in rats of varying severity according to claim 4, wherein: the dosage of the bleomycin in the model construction is 10mg/kg-80mg/kg of body weight, and the corresponding dose of the bleomycin is selected according to the severity of the required model.
6. The method of any one of claims 1 to 5, wherein the rat lung injury model with different severity induced by intratracheal spraying of bleomycin with different doses is applied to scientific research on lung injury diseases such as bronchitis, aseptic pneumonia, pulmonary fibrosis, acute lung injury and respiratory distress syndrome.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113425279A (en) * | 2021-05-27 | 2021-09-24 | 中国人民解放军总医院第八医学中心 | Animal experiment method for respiratory distress syndrome |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106214280A (en) * | 2016-07-19 | 2016-12-14 | 四川欧瑞吉生物医药股份有限公司 | A kind of Wicresoft makes the method for pulmonary fibrosis animal model |
| CN106725988A (en) * | 2016-12-01 | 2017-05-31 | 甘肃中医药大学 | A kind of rat trachea intubation procedure and its application |
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- 2020-10-14 CN CN202011093567.XA patent/CN112189625A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106214280A (en) * | 2016-07-19 | 2016-12-14 | 四川欧瑞吉生物医药股份有限公司 | A kind of Wicresoft makes the method for pulmonary fibrosis animal model |
| CN106725988A (en) * | 2016-12-01 | 2017-05-31 | 甘肃中医药大学 | A kind of rat trachea intubation procedure and its application |
Non-Patent Citations (1)
| Title |
|---|
| 周欢: "气管内喷雾注入博莱霉素诱导大鼠肺纤维化模型的建立及其评价", 《中国优秀博硕士学位论文全文数据库（硕士）》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113425279A (en) * | 2021-05-27 | 2021-09-24 | 中国人民解放军总医院第八医学中心 | Animal experiment method for respiratory distress syndrome |
| CN113425279B (en) * | 2021-05-27 | 2022-12-20 | 中国人民解放军总医院第八医学中心 | Animal experiment method for respiratory distress syndrome |
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