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高尿酸血癥疾病模型

疾病簡(jiǎn)介

尿酸(urate)是人類嘌呤化合物的終末代謝產(chǎn)物,嘌呤代謝紊亂導(dǎo)致高尿酸血癥。尿酸氧化酶(urate oxidase, UOX)基因編碼的尿酸酶(Uricase)在嘌呤的代謝過程中起重要作用,多數(shù)哺乳類動(dòng)物體內(nèi)高表達(dá)UOX,人類在進(jìn)化過程中,體內(nèi)的Uox基因沉默失活,因此嘌呤分解代謝只能生成尿酸。當(dāng)尿酸生成速度超過腎臟的排泄能力時(shí),血清的尿酸水平會(huì)顯著升高,進(jìn)而引發(fā)高尿酸血癥。

疾病模型

基于現(xiàn)有研究,南模生物建立了多種高尿酸血癥相關(guān)小鼠模型,為深入探究高尿酸血癥的發(fā)病機(jī)理、進(jìn)行藥物篩選以及評(píng)估藥物療效提供了強(qiáng)有力的工具。

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Fig.1 Detection of mouse UOX expression in Uox-KO mice by WB.?

Abbr. M, marker; WT, wild type; HO, Homozygous.

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Fig.2 Body Weight of Uox-KO mouse. Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.3 Uric acid (UA) levels of Uox-KO mouse (n=5-20). Values are expressed as mean ± SEM.?

Abbr. WT, wild type.

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Fig.4 The results of blood biochemical indicators of Uox-KO mouse (n=5-12). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.5 Observation of kidney and bladder.?

At 9 weeks of age, Uox-KO male mice had smaller kidneys with uneven surfaces compared to age-matched C57BL/6 mice. Some mice showed impaired urination, resulting in urine accumulation and bladder distention, which thinned the bladder wall.

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Fig.6 Histological analysis of kidney.?

16-week-old Uox-KO male mice revealed significant renal tubule atrophy (gray arrow), characterized by reduced volume and diminished eosinophilic cytoplasm. The interstitial space exhibited notable connective tissue proliferation (green arrow), accompanied by a substantial infiltration of lymphocytes (orange arrow) and macrophages (white arrow), with occasional necrotic cell debris (brown arrow). These features were absent in age-matched male WT mice. Scale bar=100 μm; magnification, 200×.

Abbr. WT, wild type?

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Fig.7 Effect of Allopurinol on Serum Uric Acid Levels. 12-16 week-old Uox-KO male mice were treated with Allopurinol.?

Compared to C57BL/6, serum uric acid levels of Uox-KO male mice were significantly elevated. Treatment with allopurinol (100mg/kg) significantly reduced serum uric acid levels in Uox-KO male mice (n=6-7). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.8 Kidney Function Assessment. Kidney function in Uox-KO male mice showed no significant difference compared to C57BL/6 mice (n=6-7). Values are expressed as mean ± SEM.

Abbr. WT, wild type?

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Fig.1 Body Weight of Uox-Flox/Alb-Cre mouse.

Abbr. WT, wild type.

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Fig.2 Uric acid (UA) levels of Uox-Flox/Alb-Cre mouse.?

Abbr. WT, wild type.

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Fig.3 The results of blood biochemical indicators of Uox-Flox/Alb-Cre mouse.

Abbr. WT, wild type.

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Fig.4 Histological analysis of kidney revealed no obvious micro-morphological injury in 20-week old Uox-Flox/Alb-Cre male mice.

Abbr. WT, wild type?

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Fig.5 Effect of Allopurinol on Serum Uric Acid Levels.?

6 week-old Uox-Flox/Alb-Cre male mice were treated with Allopurinol. Compared to C57BL/6, serum uric acid levels of Uox-Flox/Alb-Cre male mice were significantly elevated. Treatment with allopurinol (100mg/kg) significantly reduced serum uric acid levels in Uox-Flox/Alb-Cre male mice (n=10). Values are expressed as mean ± SEM.

Abbr. WT, wild type.

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Fig.6 Body Weight of Uox-Flox/Alb-Cre mouse.

The body weight of Uox-Flox/Alb-Cre male mice was lower compared to C57BL/6 mice. Allopurinol treatment had no effect on body weight (n=10). Values are expressed as mean ± SEM.?

Abbr. WT, wild type.

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Fig.7 Kidney Function Assessment?of Uox-Flox/Alb-Cre mouse.

Kidney function in Uox-Flox/Alb-Cre male mice showed no significant difference compared to C57BL/6 mice (n=10). Values are expressed as mean ± SEM.

Abbr. WT, wild type?

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