阅读说明：本技术 荷叶碱在制备治疗急性肾损伤药物中的应用 (Application of nuciferine in preparation of medicine for treating acute kidney injury ) 是由 谭克 樊玉梅 李丹雨 于 2019-09-30 设计创作，主要内容包括：本发明公开了一种荷叶碱在制备治疗急性肾损伤药物中的应用,伸入探讨了荷叶碱对AKI的治疗效果及抑制分子机制,进一步挖掘了荷叶碱的药理功能,拓宽了公众对荷叶碱的药效认知。(The invention discloses application of nuciferine in preparation of a medicine for treating acute kidney injury, which discusses the treatment effect and molecular inhibition mechanism of nuciferine on AKI, further develops the pharmacological function of nuciferine, and widens the public pharmaceutical effect cognition on nuciferine.)

1. Application of nuciferine in preparing medicine for treating acute renal injury is provided.

2. The use of nuciferine in the manufacture of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to reduce the amount of creatinine present in the serum.

3. The use of nuciferine in the manufacture of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to reduce the level of urea nitrogen in the serum.

4. The use of nuciferine in the preparation of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of KIM-1 mRNA expressed in the kidney.

5. The use of nuciferine in the manufacture of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of NGAL mRNA expressed in the kidney.

6. The use of nuciferine in the preparation of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of Fn14 mRNA expression in the kidney.

7. The use of nuciferine in the manufacture of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to increase the amount of klotho mRNA expression in the kidney.

8. The use of nuciferine in the preparation of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of mRNA for IL6 expressed in the kidney.

9. The use of nuciferine in the preparation of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of TNF- α mRNA expressed in the kidney.

10. The use of nuciferine in the preparation of a medicament for the treatment of acute kidney injury according to claim 1, wherein nuciferine is used to decrease the amount of fibrinectin expressed in the kidney.

Technical Field

The invention relates to the technical field of acute kidney injury, in particular to application of nuciferine in preparing a medicament for treating kidney injury.

Background

Acute Kidney Injury (AKI) is a clinically common and high-cost treatment critical condition with an increasing trend of morbidity and mortality. Acute kidney injury is mainly manifested by a sudden and sustained rapid decline in renal function and a constant accumulation of metabolites. The diagnosis index is the increase of serum creatinine (serum creatinine), and the main symptoms are oliguria or anuresis, azotemia, and water electrolyte and acid-base balance disorder. According to recent epidemiological investigations, mild, reversible acute kidney injury also leads to permanent damage of the kidney, whereas severe acute kidney injury leads to an irreversible decrease in kidney function, thereby increasing the risk and probability of death. AKI, if not effectively treated, can progress to chronic kidney disease and even directly to the end stage of renal disease.

Recent studies have shown that in the early stage of AKI, insufficient perfusion of renal blood flow leads to lethal injury of renal tubules, destruction of cytoskeletal integrity, redistribution of transport proteins and adhesion molecules, breakage of intercellular tight junctions, denudation of tubular basement membrane, as injury progresses, renal ischemia reperfusion leads to apoptosis and necrosis of tubular cells, especially in the proximal tubular segment and the thick segment of the ascending branch of the medulla loop, it is currently believed that necrosis and apoptosis of tubular epithelial cells are well-recognized inducers of AKI, and AKI-specific markers have been identified, renal injury molecule-1 (KIM-1) is a type I transmembrane glycoprotein expressed on the surface of injured cells, increased expression of KIM-1 may lead to phagocytosis of injured epithelial cells by macrophages, early stage of AKI, upregulation of KIM-1-mediated phagocytosis of injured and senescent cells may promote inflammatory responses, and KIM1 may serve as a marker of renal injury, in addition, neutrophil-associated gelatinase (nga) is a highly regulated by extracellular secretion of various renal-chemotactic factors, such as a chemotactic factors for angiogenesis, chemotactic factors for renal-1, chemotactic factors, and chemotactic factors for the generation of renal-1, and other factors, such as renal-chemotactic factors, such as renal-1-TNF-2-TNF-2-receptor, and other factors, which may be more active factors, and may be significantly expressed in various renal tubular cell-induced by various factors, and may be studied in the early stage of renal tubular cell-induced by various renal-induced by various factors.

Unfortunately, there is still no specific drug available to treat AKI at the molecular level in the clinic, and even kidney replacement surgery is required when AKI is severe; although some progress has been made in supporting treatment, survival in patients with AKI has not changed significantly.

Nuciferine (Nuciferine) is a main monomer component extracted from lotus leaves, and belongs to aporphine alkaloids. Due to the wide range of actions exhibited in food and medicine, scientists are increasingly concerned with the fundamental study of the pharmacological and molecular mechanisms of nuciferine. Nuciferine has excellent antifungal effect, and also has obvious antibacterial activity on gram-positive bacteria and acid-fast bacteria. Nuciferine can also play a role in antioxidation by removing related free radicals, enhancing enzyme activity and the like. Nuciferine antagonizes the inflammatory response through multiple pathways and genes. In the mouse macrophage RAW264.7 and microglia BV2, nuciferine inhibits LPS-induced inflammatory factor release by PPAR. Nuciferine can relieve mastitis induced by LPS by mediating TLR 4-NF-kB signal channel of mice, and can also relieve acute lung injury of mice caused by LPS by inhibiting TLR 4. In addition, the nuciferine has good effects of reducing fat and losing weight, has outstanding anti-proliferation and anti-infiltration effects on various tumor cells, and triggers the tumor cells to die. However, it is not clear whether nuciferine has an inhibitory and therapeutic effect on acute kidney injury.

Therefore, the problem to be solved by the skilled in the art is how to provide a drug for treating acute kidney injury, which uses nuciferine as a main component, and to deeply study the action mechanism of nuciferine.

Disclosure of Invention

In view of the above, the invention provides an application of nuciferine in preparation of a drug for treating acute kidney injury, which further discusses the therapeutic effect and the molecular inhibition mechanism of nuciferine on AKI, further exploits the pharmacological functions of nuciferine, and widens the public pharmacodynamic cognition on nuciferine.

In order to achieve the purpose, the invention adopts the following technical scheme:

in addition, the nuciferine can also treat the AKI by reducing the expression levels of KIM-1 mRNA, NGAL mRNA, Fn14 mRNA, Klotho mRNA, IL-6 mRNA, TNF- α mRNA and fibrinectin in the kidney.

According to the technical scheme, compared with the prior art, the invention discloses and provides the application of nuciferine in preparing the medicine for treating AKI, and researches show that nuciferine achieves the effect of treating AKI by reducing the expression quantity of mRNA of an induction factor KIM-1 of AKI in the kidney, reducing the expression quantity of mRNA of neutrophil gelatinase-associated lipocalin (NGAL) serving as a renal tubular injury marker molecule and reducing the expression quantity of mRNA of an AKI-associated inflammatory factor; on one hand, the invention provides a new application of nuciferine, and widens the application range of nuciferine; on the other hand, a theoretical basis is provided for the prevention and treatment of AKI.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 accompanying drawing is the staining of NaHCO with HE₃Staining result graphs of the group, the Folic Acid (FA) treated group, the FA + N (folic acid + nuciferine) treated group and the N (nuciferine) treated group;

FIG. 2 accompanying drawing is the detection of NaHCO by sarcosine oxidase method₃Results of serum creatinine content of mice in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown schematically;

FIG. 3 is a diagram of the detection of NaHCO by urease method₃Results of the serum urea nitrogen content of the mice in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown schematically;

FIG. 4 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the expression level of mRNA of KIM-1 in the kidney of mice in the group, FA treatment group, FA + N treatment group and N treatment group are shown schematically;

FIG. 5 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the mouse renal NGAL mRNA expression level in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown schematically;

FIG. 6 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Mice kidney in group, FA treatment group, FA + N treatment group and N treatment groupA graph showing the results of the expression level of mRNA for internal Fn 14;

FIG. 7 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the expression amount of Klotho mRNA in the kidney of mice in the group, FA treatment group, FA + N treatment group, and N treatment group are shown schematically;

FIG. 8 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the expression level of IL-6 mRNA in the kidney of the mice in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown in the figure;

FIG. 9 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the expression level of mRNA of TNF- α in the kidney of mice in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown in the figure;

FIG. 10 accompanying drawing is the detection of NaHCO by qRT-PCR method₃Results of the expression amount of mRNA of TWEAK in the kidney of the mice in the group, the FA treatment group, the FA + N treatment group and the N treatment group are shown in a schematic diagram;

FIG. 11 accompanying drawing is the detection of NaHCO by IHC method₃Results of the expression level of fibrinectin in the kidney of mice in group, FA treatment group, FA + N treatment group and N treatment group are shown schematically.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.