动物造模,药效评价,肾血管性高血压 z-bio 2024-09-19 527

　　The renal vascular hypertension model is a model that causes an increase in blood pressure due to renal artery stenosis in animals. According to different experimental methods, it can be divided into two kidney one clip type (left renal artery stenosis, bilateral kidney preservation), one kidney one clip type (left renal artery stenosis, right kidney resection), and two kidney two clip type (bilateral renal artery stenosis, bilateral kidney preservation).

　　(1) The replication method can be used to create models in dogs, rabbits, and rats. After routine anesthesia, the animal is fixed in a supine position. Aseptic surgery is performed to open the abdominal cavity, and the left renal artery is carefully separated. A U-shaped silver clip or Q-shaped silver ring is placed over the renal artery. The diameter of the ring used for dogs weighing 6-8 kg is 0.8-1.2mm, for rabbits it is 0.5-0.8mm, and for rats weighing 150-200g it is 0.2-0.25mm. It is recommended to reduce blood flow by 50% -70% after narrowing. The contralateral kidney can be preserved, removed, or subjected to renal artery stenosis according to experimental requirements. Alternatively, if the animal's blood pressure is deemed unsatisfactory after the first surgery, a second surgery can be performed to remove the contralateral kidney or narrow the renal artery. Generally, animals with a systolic blood pressure greater than 160mmHg (21.3kPa) after 6 weeks are considered as having renal vascular hypertension. Animal surgery generally uses a dorsal spinal incision, but there are also reports advocating the use of a midline abdominal incision. The specific method is as follows:

　　After anesthesia, the dog can be fixed in a prone position, with a sandbag placed under the abdomen to support the back. Starting from 1.5-2cm beside the spine, a 4cm long skin incision is made on the left side about two fingers wide from the rib margin (right side along the rib margin). Cut open the subcutaneous tissue and the abdominal and dorsal fascia in sequence, and cut open the internal oblique fascia next to the junction of the internal and external oblique fascia. Push open the long dorsal muscle and cut open the transverse abdominal muscle covering the kidneys along the muscle fibers to separate the muscles. Use your fingers to touch the kidney through the surgical area and locate the renal artery. Carefully and bluntly separate a section of the renal artery according to the required length, use a silver clip of appropriate size to cover the renal artery, and finally suture the surgical incision layer by layer. Antibiotics can be administered continuously for one week after surgery. If making an abdominal incision, push open the intestinal tract to expose the kidneys. The surgical methods for rats are basically the same.

　　(2) The characteristics of the model are that within a certain time range, the rate and degree of blood pressure increase in animals are directly proportional to the degree of arterial stenosis. If renal artery stenosis is not sufficient, animals cannot develop hypertension or only develop transient hypertension; If it is excessively narrow, it can easily cause kidney necrosis, and animals may die due to severe renal dysfunction, or the loss of unilateral renal function and complete compensation of contralateral renal function without the formation of hypertension. Adult animals should be used for surgery, as using young animals can easily cause renal artery stenosis and renal necrosis. When separating the renal artery, attention should be paid to whether there are branches. If only the renal artery branch is narrowed, it cannot cause hypertension.

　　(3) Comparative medical renal artery stenosis can cause renal ischemia, leading to increased synthesis and secretion of renin in the kidneys, which in turn increases the level of angiotensin in the blood and raises blood pressure. The renal vascular hypertension model is a commonly used hypertension model, which is relatively simple to operate, stable in hypertension, and has many similarities in pathophysiology with human hypertension. Its response to antihypertensive drugs is consistent with that of hypertensive patients, and it is suitable for screening antihypertensive drugs and evaluating their efficacy.