作者：赵伟1 ，张瑶1，2 ，唐荣杰1，2 ，霍迎新1，2 ，廉秋芳1，2

单位：

1.712000陕西省咸阳市，延安大学咸阳医院心血管内科　2.716000陕西省延安市，延安大学医学院

Units：

1.Department of Cardiology, Xianyang Hospital of Yan'an University, Xianyang 712000, China 2.Medical School of Yan'an University, Yan'an 716000, China

关键词：

高血压；盐敏感性高血压；肾脏；Klotho；血管紧张素Ⅱ 1型受体

Keywords：

Hypertension; Salt sensitive hypertension; Kidney; Klotho; Angiotensin Ⅱ type 1 receptor

CLC：

R 544.1

DOI：

10.12114/j.issn.1008-5971.2024.00.038

Funds：

国家自然科学基金资助项目（82160090）；陕西省重点研发计划项目（2023-YBSF-636）；咸阳市中医药科研项目 （XYWJ-ZYKY-2023-008）

摘要：

目的　基于Klotho/血管紧张素Ⅱ 1型受体（AT1R）信号通路探讨大蒜素对盐敏感性高血压（SSH） 模型大鼠肾脏的影响。方法　本实验时间为2022年2—6月。将24只健康SPF级Dahl盐敏感大鼠随机分为正常盐组、高 盐组和高盐＋大蒜素组，每组8只。正常盐组大鼠给予0.3%氯化钠饲料喂养。高盐组和高盐＋大蒜素组大鼠给予8% 氯化钠饲料喂养以制备SSH模型，在此基础上，高盐＋大蒜素组大鼠给予大蒜素16 mg/kg口服。三组大鼠均干预4周。 比较三组大鼠干预前及干预1、2、3、4周尾动脉收缩压，干预4周后肾功能指标〔尿蛋白、血肌酐及肾脏重量/体质量 （KW/BW）比值〕、肾组织病理学改变、氧化应激指标〔丙二醛、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）水 平〕和肾组织Klotho、AT1R表达水平及其mRNA、蛋白相对表达量。结果　干预1周，高盐组大鼠尾动脉收缩压高于正 常盐组（P＜0.05）；干预2、3、4周，高盐组大鼠尾动脉收缩压高于正常盐组，高盐＋大蒜素组大鼠尾动脉收缩压低 于高盐组（P＜0.05）。干预4周后，高盐组大鼠尿蛋白、血肌酐、KW/BW比值高于正常盐组，高盐＋大蒜素组大鼠尿 蛋白、血肌酐、KW/BW比值低于高盐组（P＜0.05）。HE染色结果显示，与正常盐组相比，高盐组大鼠肾间质伴有炎 症浸润；与高盐组相比，高盐＋大蒜素组大鼠肾脏病理损伤相对减轻，局部可见少量炎症细胞浸润。Masson染色结果 显示，与正常盐组相比，高盐组视野内观察到大量胶原纤维沉积，肾组织纤维化严重；与高盐组相比，高盐＋大蒜素 组大鼠肾组织纤维化明显减轻。干预4周后，高盐组大鼠肾组织丙二醛水平高于正常盐组，肾组织SOD、GSH水平低于 正常盐组（P＜0.05）；干预4周后，高盐＋大蒜素组肾组织丙二醛水平低于高盐组，肾组织SOD、GSH水平高于高盐 组（P＜0.05）。干预4周后，高盐组大鼠肾组织Klotho表达水平及其mRNA、蛋白相对表达量低于正常盐组，AT1R表 达水平及其mRNA、蛋白相对表达量高于正常盐组（P＜0.05）；干预4周后，高盐＋大蒜素组大鼠肾组织Klotho表达水 平及其mRNA、蛋白相对表达量高于高盐组，AT1R表达水平及其mRNA、蛋白相对表达量低于高盐组（P＜0.05）。结 论　大蒜素能有效改善SSH模型大鼠肾功能，减轻其肾组织损伤、胶原纤维沉积及肾脏氧化应激损伤，其机制可能与 大蒜素调控Klotho/AT1R信号通路有关。

Abstract：

Objective To investigate the effect of allicin on kidney of salt sensitive hypertension (SSH) model rats based on Klotho/ angiotensin Ⅱ type 1 receptor (AT1R) signaling pathway. Methods The experiment was conducted from February to June 2022. Twenty-four healthy SPF Dahl salt-sensitive rats were randomly divided into normal salt group, high salt group and high salt+allicin group, with 8 rats in each group. Rats in the normal salt group were fed with 0.3% sodium chloride. The rats in the high salt group and the high salt+allicin group were fed with 8% sodium chloride to prepare SSH model. On this basis, the rats in the high salt+allicin group were given allicin 16 mg/kg orally. Three groups of rats were intervened for 4 weeks. The systolic blood pressure of the tail artery before intervention and at 1, 2, 3, 4 weeks after intervention, renal function indexes urine protein, serum creatinine and kidney weight/body weight (KW/BW) ratio] , pathological changes of renal tissue, oxidative stress indexes [levels of malondialdehyde, superoxide dismutase (SOD) and glutathione (GSH) ] , and expression levels, mRNA relative expression, protein relative expression of Klotho and AT1R of renal tissue at 4 weeks after intervention were compared among the three groups. Results At 1 week after intervention, the systolic blood pressure of the tail artery in the high salt group was higher than that in the normal salt group (P < 0.05) . At 2, 3 and 4 weeks after intervention, the systolic blood pressure of the tail artery in the high salt group was higher than that in the normal salt group, and the systolic blood pressure of the tail artery in the high salt+allicin group was lower than that in the high salt group (P < 0.05) . At 4 weeks after intervention, the urine protein, serum creatinine and KW/BW ratio in the high salt group were higher than those in the normal salt group, and those in the high salt+allicin group were lower than those in the high salt group (P < 0.05) . HE staining results showed that, compared with the normal salt group, the renal interstitium of the high salt group was accompanied by inflammatory infiltration; compared with the high-salt group, the renal pathological damage in the high-salt+allicin group was relatively reduced, and a small amount of inflammatory cell infiltration was observed locally. Masson staining results showed that compared with the normal salt group, a large amount of collagen fiber deposition was observed in the high salt group, and the renal tissue fibrosis was serious; compared with the high-salt group, the renal fibrosis in the high-salt+allicin group was significantly reduced. At 4 weeks after intervention, the level of malondialdehyde of renal tissue in high salt group was higher than that in normal salt group, and the levels of SOD and GSH of renal tissue were lower than those in normal salt group (P < 0.05) . At 4 weeks after intervention, the level of malondialdehyde of renal tissue in high salt+allicin group was lower than that in high salt group, and the levels of SOD and GSH of renal tissue were higher than those of high salt group (P < 0.05) . At 4 weeks after intervention, expression levels, mRNA relative expression, protein relative expression of Klotho of renal tissue in high salt group were lower than those in normal salt group, while expression levels, mRNA relative expression, protein relative expression of AT1R of renal tissue were higher than those in normal salt group (P < 0.05) . At 4 weeks after intervention, the expression levels, mRNA relative expression, protein relative expression of Klotho of renal tissue in high salt+allicin group were higher than those in high salt group, while expression levels, mRNA relative expression, protein relative expression of Klotho AT1R of renal tissue were lower than those in high salt group ( P < 0.05) . Conclusion Allicin can effectively improve the renal function of SSH model rats, reduce renal tissue damage, collagen fiber deposition and renal oxidative stress injury. The mechanism may be related to the regulation of Klotho/AT1R signaling pathway by allicin.

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