姜黃素固體脂質(zhì)納米粒對心腎綜合征模型大鼠心、腎、肺功能及細胞自噬相關(guān)因子表達的影響

李旭 郝迪 劉偉偉 王梓 史鵬程 李楠

中圖分類號 R965 文獻標志碼 A 文章編號 1001-0408（2021）19-2347-07

DOI 10.6039/j.issn.1001-0408.2021.19.07

摘 要 目的：研究姜黃素固體脂質(zhì)納米粒（Cur-SLN）對心腎綜合征模型大鼠心、腎、肺功能及細胞自噬相關(guān)因子表達的影響。方法：將大鼠分為假手術(shù)組、模型組、雷帕霉素組（陽性對照，2 mg/kg）和Cur-SLN低、高劑量組（5、10 mg/kg），除模型組13只大鼠外（其中3只用于判斷是否造模成功），其余各組10只。除假手術(shù)組外，其余各組大鼠均采用腹主動脈縮窄合并腎急性缺血再灌注損傷法復制心腎綜合征模型。造模成功后，各給藥組大鼠均尾靜脈注射相應(yīng)藥物，假手術(shù)組和模型組大鼠注射等體積生理鹽水，每天1次，連續(xù)4周。末次注射24 h后，檢測大鼠血清中血管緊張素轉(zhuǎn)換酶（ACE）、游離三碘甲狀腺原氨酸（FT3）及精氨酸加壓素（AVP）的含量;觀察大鼠心臟、腎、肺組織的病理學形態(tài);檢測大鼠心臟、腎、肺組織中LC3、Beclin-1蛋白的分布情況和表達水平。結(jié)果：與假手術(shù)組比較，模型組大鼠血清中ACE、FT3含量，心臟、腎指數(shù)以及心臟、腎、肺組織中LC3（腎組織中除外）、Beclin-1蛋白的表達水平均顯著升高（P<0.01），AVP含量和肺指數(shù)均顯著降低（P<0.01）;心臟非梗死區(qū)心肌細胞明顯肥大、心肌纖維排列紊亂，腎非梗死區(qū)腎小管結(jié)構(gòu)紊亂、呈囊性擴張，肺泡可見明顯炎性細胞浸潤;心臟、腎、肺組織中LC3、Beclin-1蛋白的陽性表達均增多，主要分布于心肌細胞的細胞質(zhì)、遠端腎小管上皮細胞和肺泡巨噬細胞、上皮細胞中。與模型組比較，Cur-SLN各劑量組大鼠上述指標大部分顯著逆轉(zhuǎn);心臟、腎、肺組織的病理改變程度均減輕，炎性細胞浸潤減少，且LC3、Beclin-1蛋白的陽性表達均減少，主要分布于心肌細胞細胞質(zhì)、近端腎小管上皮細胞中，少數(shù)分布于遠端腎小管上皮細胞和肺泡巨噬細胞、上皮細胞中。結(jié)論：Cur-SLN 可改善心腎綜合征模型大鼠的心、腎、肺功能，其作用機制可能與調(diào)控LC3、Beclin-1蛋白在心臟、腎、肺組織的分布或表達有關(guān)。

關(guān)鍵詞 姜黃素;固體脂質(zhì)納米粒;心腎綜合征;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.