Application of paeonol in preparation of medicine for treating lupus nephritis

Abstract

The invention provides an application of paeonol in preparation of a medicine for treating lupus nephritis, the structural formula of the paeonol is as shown in the specification, and the invention also provides an application of the paeonol in preparation of a medicine for inhibiting renal fibrosis caused by lupus nephritis. Experiments show that paeonol can relieve fibrosis of lupus nephritis and reduce the autoantibody level, and a new method is provided for treating lupus nephritis.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine and relates to a medicine for treating lupus nephritis, specifically to the use of paeonol in preparing a medicine for treating lupus nephritis. Background Art

[0002] Lupus nephritis (LN) refers to a disease in which systemic lupus erythematosus (SLE) is combined with immune damage of different pathological types in both kidneys, accompanied by obvious clinical manifestations of kidney damage. Its pathogenesis involves the formation of immune complexes, abnormal activation of immune cells, and imbalance of cytokines. The pathological characteristics of this disease include kidney damage caused by the deposition of immune complexes, as well as the inflammatory response and tissue destruction caused by these deposits. In addition to the systemic manifestations of SLE, clinically, LN manifests as symptoms such as hematuria, proteinuria, and renal insufficiency, which can gradually worsen with repeated attacks of the disease and eventually lead to chronic renal failure. Therefore, the treatment goals of LN are to control the activity of the disease, protect kidney function, and delay the progression of renal tissue fibrosis.

[0003] Although the application of glucocorticoids and immunosuppressants has made certain progress in controlling LN disease activity and delaying disease progression, some patients still cannot achieve remission after treatment, or relapse after remission and eventually progress to end-stage renal disease. At the same time, complications such as lipid metabolism disorders, gastrointestinal ulcers, osteoporosis, and secondary infections caused by existing treatment regimens also seriously affect patients' quality of life and prognosis.

[0004] As an important source of clinical drugs, the safety and effectiveness of Chinese medicine monomers are widely recognized. Studies have shown that some Chinese medicine monomers have the characteristics of anti-oxidation, anti-inflammatory, and inhibition of fibrosis, and have a certain protective effect on kidney damage. However, the molecular targets and mechanisms of action of many Chinese medicine monomers in the treatment of kidney disease are still unclear, which is also the difficulty in developing drugs for the treatment of kidney disease based on Chinese medicine monomers. Summary of the invention

[0005] In view of the above technical problems in the prior art, the present invention provides the use of paeonol in the preparation of a drug for treating lupus nephritis, which is intended to solve the technical problem that the drugs in the prior art are not effective in treating lupus nephritis, especially renal fibrosis caused by lupus nephritis.

[0006] The present invention provides the use of paeonol in preparing a medicine for treating lupus nephritis. The structural formula of the paeonol is shown below:

[0007]

[0008] The present invention also provides the use of paeonol in preparing a drug for inhibiting renal fibrosis caused by lupus nephritis. The structural formula of the paeonol is shown below:

[0009]

[0010] The present invention provides a Chinese medicine monomer paeonol for inhibiting lupus nephritis and renal fibrosis caused by it. Experiments have found that paeonol can alleviate lupus nephritis fibrosis and reduce the level of autoantibodies, thus providing a new method for treating lupus nephritis.

[0011] Compared with the existing technology, the technical effect of the present invention is positive and obvious, and compared with the compound Chinese medicine, it has better controllability of drug efficacy and efficacy evaluation. In addition, the Chinese medicine monomer paeonol is used to treat lupus nephritis, which has a wide source, low cost, good efficacy, no kidney toxicity and side effects, and is conducive to long-term treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 The figure shows that paeonol improves the autoantibody levels of mice with lupus nephritis: serum anti-double-stranded DNA (dsDNA) antibody levels (upper figure) and anti-nuclear antibody levels (lower figure) of mice in the control group (Mpj), model group (Lpr), and paeonol treatment group (Pae).

[0013] Figure 2 The figure shows that paeonol improves renal function and urine protein levels in mice with lupus nephritis: serum creatinine levels (upper figure), urea nitrogen (middle figure) and urine protein / urine creatinine levels (lower figure) of mice in the control group (Mpj), model group (Lpr) and paeonol treatment group (Pae).

[0014] Figure 3 The results show that paeonol improves renal pathological changes in mice with lupus nephritis: hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) pathological staining of renal tissue of mice in the control group (Mpj), model group (Lpr) and paeonol-treated group (Pae) ​​(upper figure), PAS staining activity score (lower figure, left) and chronicity score (lower figure, right).

[0015] Figure 4 The results showed that paeonol improved renal fibrosis in mice with lupus nephritis: immunochemical staining of type I collagen (CollagenI), type IV collagen (CollagenIV) and α-smooth muscle actin (α-SMA) in the renal tissue of mice in the control group (Mpj), model group (Lpr) and paeonol treatment group (Pae).

[0016] Figure 5The results show that paeonol improves renal immunoglobulin and complement deposition in mice with lupus nephritis: immunofluorescence staining of immunoglobulin IgG, immunoglobulin IgM and complement component C3 in the renal tissue of mice in the control group (Mpj), model group (Lpr) and paeonol treatment group (Pae). DETAILED DESCRIPTION

[0017] Example 1

[0018] 1. Animal model of lupus nephritis and experimental groups

[0019] MRL / Lpr lupus model mice with spontaneous disease (purchased from Shanghai Slake Experimental Animal Co., Ltd.) were selected. When there was no disease in the 8th week, the Lpr mice were divided into a model group and a paeonol (purchased from Targetmol) treatment group, and MRL / Mpj mice with the same background (purchased from Shanghai Slake Experimental Animal Co., Ltd.) were used as controls. Paeonol was dissolved in DMSO + sterile saline with a mass percentage concentration of 5%, and administered intraperitoneally at a dose of 30 mg / kg, once every other day, for 12 weeks. The control group and the model group were given an equal amount of DMSO + sterile saline with a mass percentage concentration of 5%. At the end of the administration, the mice were anesthetized with sodium pentobarbital with a mass percentage concentration of 0.1%, and blood and kidney tissue were collected.

[0020] 2. Experimental Methods

[0021] The level of mouse serum autoantibodies was detected by ELISA. The urine protein and urine creatinine levels of each group of animals were detected using a kit, and the urine protein to creatinine ratio (UPCR), blood creatinine (Cr), and blood urea nitrogen (BUN) levels were calculated. The pathological changes of mouse renal tissue were observed by HE staining and PAS staining, the changes of mouse renal fibrosis were observed by immunohistochemistry, and the deposition of mouse renal immunoglobulins was observed by immunofluorescence.

[0022] 3. Experimental Results

[0023] 1. Paeonol improves the autoantibody levels in mice with lupus nephritis.

[0024] The levels of anti-double-stranded DNA antibodies and anti-nuclear antibodies in lupus nephritis mice were significantly higher than those in the control group, while the levels of these two autoantibodies in the paeonol (Pae) ​​treatment group were significantly lower than those in the model group, indicating that paeonol can effectively improve the systemic disease activity of lupus mice (see Figure 1 ).

[0025] 2. Paeonol improves renal function and urine protein levels in mice with lupus nephritis.

[0026] The serum urea nitrogen, serum creatinine, and urine protein / urine creatinine levels of lupus nephritis mice were significantly higher than those of the control group, while they were significantly decreased after paeonol (Pae) ​​treatment, indicating that paeonol can effectively improve the renal function and urine protein level of lupus nephritis mice (see Figure 2 ).

[0027] 3. Paeonol alleviates renal pathological changes in mice with lupus nephritis.

[0028] The renal pathological manifestations of lupus nephritis mice were active lesions such as endothelial cell proliferation, neutrophil infiltration, platinum ear-like structures and cellular crescents, and chronic lesions such as glomerular sclerosis and fibrous crescents. After treatment with paeonol (Pae), both the activity and chronicity scores were significantly reduced, indicating that paeonol can effectively improve the pathological structural changes at the anatomical morphological level of the kidneys of lupus nephritis mice (see Figure 3 ).

[0029] 4. Paeonol alleviates renal fibrosis changes in mice with lupus nephritis.

[0030] Immunohistochemical staining of Collagen I, Collagen IV and α-SMA in the kidneys showed that the deposition of collagen fibers and the increase of fibroblasts in the glomeruli and interstitium of mice with lupus nephritis were increased, while these were significantly reduced after paeonol (Pae) ​​treatment, indicating that paeonol can effectively improve the fibrotic lesions in the kidneys of mice with lupus nephritis (see Figure 4 ).

[0031] 5. Paeonol reduces the deposition of immunoglobulin and complement in the kidneys of mice with lupus nephritis.

[0032] Immunofluorescence staining of IgG (red fluorescence), IgM (green fluorescence) and complement C3 (red fluorescence) in the kidneys showed that the deposition of immunoglobulins and complement in the glomeruli of mice with lupus nephritis increased and concentrated in multiple locations such as the mesangial area in the form of granules or clumps, while these were significantly reduced after treatment with paeonol (Pae), indicating that paeonol can effectively improve the deposition of immunoglobulins and complement in mice with lupus nephritis (see Figure 5 ).

Claims

1. Use of paeonol in preparing a drug for treating lupus nephritis, wherein the structural formula of paeonol is as follows:

2. Use of paeonol in the preparation of a drug for inhibiting renal fibrosis caused by lupus nephritis. The structural formula of the paeonol is shown below:

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