Article: [Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on AngⅡ-induced cardiomyocyte hypertrophy].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
2024 Volume 49, Issue 3, Page(s) 754–762
Abstract: This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro ... ...
Abstract | This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 μmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function. |
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MeSH term(s) | Rats ; Animals ; Myocytes, Cardiac ; Cells, Cultured ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism ; Atrial Natriuretic Factor/genetics ; Atrial Natriuretic Factor/metabolism ; Angiotensin II/adverse effects ; Angiotensin II/metabolism ; Natriuretic Peptide, Brain/metabolism ; Hypertrophy/metabolism ; Cardiomegaly/chemically induced ; Cardiomegaly/drug therapy ; Cardiomegaly/genetics |
Chemical Substances | Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Atrial Natriuretic Factor (85637-73-6) ; Angiotensin II (11128-99-7) ; Natriuretic Peptide, Brain (114471-18-0) |
Language | Chinese |
Publishing date | 2024-03-11 |
Publishing country | China |
Document type | English Abstract ; Journal Article |
ZDB-ID | 1004649-5 |
ISSN | 1001-5302 ; 0254-0029 |
ISSN | 1001-5302 ; 0254-0029 |
DOI | 10.19540/j.cnki.cjcmm.20231020.401 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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