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動(dòng)脈粥樣硬化疾病模型

疾病簡(jiǎn)介

動(dòng)脈粥樣硬化(atherosclerosis,AS)是一種以脂質(zhì)代謝紊亂為特征的慢性炎癥性血管疾病。它的主要病理特點(diǎn)是在大中型動(dòng)脈的內(nèi)膜及其中膜形成脂質(zhì)條紋和粥樣斑塊,最終使血管腔變窄甚至阻塞。作為冠心病、腦梗死、外周血管病的主要原因,動(dòng)脈粥樣硬化導(dǎo)致的死亡率居高不下。

疾病模型

南模生物代謝平臺(tái)建立了多種動(dòng)脈粥樣硬化小鼠模型,為深入探究動(dòng)脈粥樣硬化的發(fā)病機(jī)理、藥物篩選以及評(píng)估藥物療效提供了強(qiáng)有力的工具。

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Fig.1 Lipid profile biochemical markers of male Apoe-KO mice and? WT mice CD conditions.?

Under CD conditions, male Apoe-KO mice exhibit elevated levels of total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) compared to WT mice, while high-density lipoprotein cholesterol (HDL-C) levels are decreased. (n=5-10).

Abbr. WT, wild type; CD, chow diet.

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Fig.2 Oil Red O staining of aortic valve in male Apoe-KO mice and WT mice under CD conditions.?

The results indicate that no lipid accumulation was observed in the aortic valves of WT mice at 7 months of age. In contrast, all Apoe-KO mice (6/6) exhibited significant lipid accumulation in the aortic valves as early as 5 months of age, with the severity of this phenotype progressively worsening with age. (n=4-6).?

Abbr. WT, wild type; CD, chow diet.

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Fig.3 Oil Red O staining of aorta in male Apoe-KO mice and WT mice under CD conditions.?

The results indicate that at 5 months of age, WT mice exhibit no significant lesions in the aorta, while some Apoe-KO mice (4/6) show fat accumulation near the aortic arch. By 6 to 7 months of age, all Apoe-KO mice (4/4) exhibit fat accumulation, with the severity of this phenotype progressively increasing. (n=4-6).

Abbr. WT, wild type; CD, chow diet.

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Fig.4 Masson staining of aortic valve in Apoe-KO mice and WT mice under CD conditions.?

Muscle fibers appear red, while collagen fibers are stained blue. Apoe-KO mice exhibit increased collagen content within plaques, suggesting enhanced plaque stability. (n=3).?

Abbr. WT, wild type; CD, chow diet.

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Fig.5 Representative pictures of aortic valve.?

In WT mice, no significant plaque formation, necrosis, or inflammatory cell infiltration is seen. However, in Apoe-KO mice, extensive plaque formation is observed in the aortic valve, protruding into the lumen. Numerous interwoven collagen fibers are present, along with abundant infiltration of foam cells (red arrows). A small amount of cholesterol crystals (black arrows), appearing as needle-shaped voids, are visible, accompanied by minor deposits of brown pigment (green arrows). A small number of infiltrating lymphocytes (yellow arrows) are also noted. Myocardial cells display loose and irregular arrangement. The black box indicates the location of the magnified view.

Abbr. WT, wild type; CD, chow diet.

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Fig.1 The body weight curve of male Apoe-KO mice and WT mice under WD(western diet) conditions. (n=10~15).

Abbr. WT, wild type; WD, western diet.

Note. WD started at 6 weeks of age.

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Fig.2 Lipid profile biochemical markers of male Apoe-KO mice and WT mice under WD conditions.?

Under WD conditions, male Apoe-KO mice exhibit elevated levels of triglycerides (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) compared to WT mice, while high-density lipoprotein cholesterol (HDL-C) levels are decreased. (n=7~15).?

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Fig.3 Oil Red O staining of aortic valve in male Apoe-KO mice and WT mice under WD conditions.

The results indicate that no lipid accumulation was observed in the aortic valves of WT mice at 17 weeks of WD. In contrast, all Apoe-KO mice (3/3) exhibited significant lipid accumulation in the aortic valves as early as 7 weeks of WD, with the severity of this phenotype progressively worsened with age. (n=3~5).?

Abbr. WT, wild type; WD, western diet.

Note. WD started at 6 weeks of age.

image.png

Fig.4 Oil Red O staining of aorta in male Apoe-KO mice and WT mice under WD conditions.?

The results indicate that after 17 weeks of WD, WT mice exhibit no significant lesions in the aorta, while all Apoe-KO mice (3/3) show fat accumulation near the aortic arch after 7 weeks of WD. By 17 weeks of WD, the severity of this phenotype progressively increasing. (n=3~5).

Abbr. WT, wild type; WD, high-fat diet.

Note. WD started at 6 weeks of age.

image.png

Fig.5 Masson staining of aortic valve in Apoe-KO mice and WT mice under WD conditions.?

Muscle fibers appear red, while collagen fibers are stained blue. Apoe-KO mice exhibit increased collagen content, suggesting enhanced plaque stability. (n=3).?

Abbr. WT, wild type; WD, high-fat diet.

Note. WD started at 6 weeks of age.

image.png

Fig.6 Representative pictures of aortic valve.?

In WT mice after 17 weeks of WD feeding, the vascular intima of cardiac tissue appears smooth with no plaque formation. Myocardial cells are loosely arranged, and occasional perivascular lymphocyte infiltration is noted (red arrows). In contrast, ApoE-KO mice after 7 week of WD feeding display extensive plaques (yellow arrows) within the vessels, protruding into the lumen, with fibrous connective tissue (brown arrows) and minimal foam cell accumulation (blue arrows) on the surface. Needle-like clefts (orange arrows), likely cholesterol crystals, and necrotic debris (black arrows) are seen within the plaques. Lymphocyte infiltration (red arrows) and fibrous tissue proliferation (purple arrows) are present in the interstitial space. The black box indicates the magnified region.

Abbr. WT, wild type; WD, high-fat diet.

Note. WD started at 6 weeks of age.

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