姜黄素固体脂质纳米粒对心肾综合征模型大鼠心、肾、肺功能及细胞自噬相关因子表达的影响

李旭 郝迪 刘伟伟 王梓 史鹏程 李楠

中圖分类号 R965 文献标志码 A 文章编号 1001-0408（2021）19-2347-07

DOI 10.6039/j.issn.1001-0408.2021.19.07

摘 要 目的：研究姜黄素固体脂质纳米粒（Cur-SLN）对心肾综合征模型大鼠心、肾、肺功能及细胞自噬相关因子表达的影响。方法：将大鼠分为假手术组、模型组、雷帕霉素组（阳性对照，2 mg/kg）和Cur-SLN低、高剂量组（5、10 mg/kg），除模型组13只大鼠外（其中3只用于判断是否造模成功），其余各组10只。除假手术组外，其余各组大鼠均采用腹主动脉缩窄合并肾急性缺血再灌注损伤法复制心肾综合征模型。造模成功后，各给药组大鼠均尾静脉注射相应药物，假手术组和模型组大鼠注射等体积生理盐水，每天1次，连续4周。末次注射24 h后，检测大鼠血清中血管紧张素转换酶（ACE）、游离三碘甲状腺原氨酸（FT3）及精氨酸加压素（AVP）的含量;观察大鼠心脏、肾、肺组织的病理学形态;检测大鼠心脏、肾、肺组织中LC3、Beclin-1蛋白的分布情况和表达水平。结果：与假手术组比较，模型组大鼠血清中ACE、FT3含量，心脏、肾指数以及心脏、肾、肺组织中LC3（肾组织中除外）、Beclin-1蛋白的表达水平均显著升高（P<0.01），AVP含量和肺指数均显著降低（P<0.01）;心脏非梗死区心肌细胞明显肥大、心肌纤维排列紊乱，肾非梗死区肾小管结构紊乱、呈囊性扩张，肺泡可见明显炎性细胞浸润;心脏、肾、肺组织中LC3、Beclin-1蛋白的阳性表达均增多，主要分布于心肌细胞的细胞质、远端肾小管上皮细胞和肺泡巨噬细胞、上皮细胞中。与模型组比较，Cur-SLN各剂量组大鼠上述指标大部分显著逆转;心脏、肾、肺组织的病理改变程度均减轻，炎性细胞浸润减少，且LC3、Beclin-1蛋白的阳性表达均减少，主要分布于心肌细胞细胞质、近端肾小管上皮细胞中，少数分布于远端肾小管上皮细胞和肺泡巨噬细胞、上皮细胞中。结论：Cur-SLN 可改善心肾综合征模型大鼠的心、肾、肺功能，其作用机制可能与调控LC3、Beclin-1蛋白在心脏、肾、肺组织的分布或表达有关。

关键词 姜黄素;固体脂质纳米粒;心肾综合征;自噬

Effects of Curcumin Solid Lipid Nanoparticles on Cardiac， Renal and Pulmonary Functions and the Expression of Autophagy Related Factors in Cardiorenal Syndrome Model Rats

LI Xu，HAO Di，LIU Weiwei，WANG Zi，SHI Pengcheng，LI Nan（Tianjin Institute for Medical and Pharmaceutical Science， Tianjin 300020， China）

ABSTRACT   OBJECTIVE： To study the effects of Curcumin solid lipid nanoparticels （Cur-SLN） on cardiac， renal and pulmonary functions， the expression of autophagy related factors in cardiorenal syndrome model rats. METHODS： The rats were divided into sham operation group， model group， rapamycin group （positive control， 2 mg/kg）， Cur-SLN low-dose and high-dose groups （5， 10 mg/kg）， except for 13 rats in the model group（3 of which are used to judge whether modeling is successful）， 10 rats in the other groups. Except for sham operation group， cardiorenal syndrome of other groups were induced by abdominal aortic coarctation combined with acute renal ischemia-reperfusion injury. After successful modeling， rats in each administration group were injected with corresponding drugs through caudal vein， and rats in sham operation group and model group were injected with equal volume normal saline ，once a day for 4 weeks. Twenty-four hours after the last administration， the contents of angiotensin converting enzyme （ACE）， free triiodothyronine （FT3） and arginine vasopressin （AVP） in rat serum were detected. The pathological morphology of rat heart， kidney and lung were observed. The distribution and expression of LC3 and Beclin-1 protein in rat heart， kidney and lung were detected. RESULTS： Compared with sham operation group， the contents of ACE and FT3 in serum， the indexes of heart and kidney， the expression of LC3 （except in renal tissue） and Beclin-1 protein in heart， kidney and lung were significantly increased （P<0.01）， and the contents of AVP and lung index were decreased significantly （P<0.01）; myocardial cells in the non-infarcted area of the heart were obviously hypertrophic， the arrangement of myocardial fibers was disordered; the structure of renal tubules in the non-infarcted area of the kidney was disordered; and there was cystic expansion and obvious inflammatory cell infiltration in the alveoli; positive expression of LC3 and Beclin-1 protein in heart， kidney and lung increased， mainly distributed in the cytoplasm of cardiomyocytes， distal renal tubular epithelial cells， alveolar macrophages and epithelial cells. Compared with model group， the above indexes of rats in each dose group of Cur-SLN were mostly significantly reversed; the pathological changes of heart， kidney and lung tissues were reduced， the infiltration of inflammatory cells was reduced; and the positive expression of LC3 and Beclin-1 protein were reduced， which were mainly distributed in the cytoplasm of cardiomyocytes and proximal renal tubular epithelial cells， and a few in distal renal tubular epithelial cells， alveolar macrophages and epithelial cells. CONCLUSIONS： Cur-SLN can improve the heart， kidney and lung functions of rats with cardiorenal syndrome， and its mechanism may be related to regulating the distribution or expression of LC3 and Beclin-1 protein in heart， kidney and lung.