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DP1 used as senile hypertension immunotherapy drug target and application of DP1

A technology for senile and high blood pressure, which can be used in drug combinations, pharmaceutical formulations, cardiovascular system diseases, etc., and can solve problems such as unclear effects.

Inactive Publication Date: 2020-03-27
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A large number of studies have shown that T cells in the elderly can secrete a large amount of IFNγ and TNFα after activation. It is known that gene knockout of TNFα or IFNγ can inhibit the hypertensive response induced by AngⅡ. The role of inflammatory cells is not yet clear, so far no inflammatory cells through the surface protein DP1 (PGD 2 Receptor) involved in the occurrence and development of senile hypertension and related mechanisms

Method used

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  • DP1 used as senile hypertension immunotherapy drug target and application of DP1
  • DP1 used as senile hypertension immunotherapy drug target and application of DP1
  • DP1 used as senile hypertension immunotherapy drug target and application of DP1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0135] Example 2 Conditional deletion of DP1 T cells enhances aging-related blood pressure elevation, Th1 activation and tissue remodeling in mice.

[0136] The main experimental parts involved in this embodiment are as follows:

[0137] 1. RT-PCR detection of DP1 gene expression

[0138] Method is with the PCR detection of embodiment 1 cytokine, and the results are shown in image 3 A. Figure 5 a.

[0139] 2. Blood pressure telemetry in mice

[0140] 1) Soak the decontaminated implant in sterile saline for at least 15 minutes.

[0141] 2) The mice to be tested were anesthetized by intraperitoneal injection of Avertin.

[0142] 3) Depilate the neck and back of the mouse with depilatory cream, and then disinfect the depilated parts with 75% medical alcohol.

[0143] 4) Use a sterile scalpel to make a 2-3 cm incision along the midline of the neck to expose the mandibular gland. In addition, a small opening of appropriate size was made in the depilated area of ​​the back ...

Embodiment 3

[0202] Example 3 IFNr deficiency or TNFa neutralization can reduce aging-related blood pressure and reactive oxygen species production in TDP1KO mice.

[0203] The main experimental parts involved in this embodiment are as follows:

[0204] 1. Detection of Th1 factor levels in peripheral blood of mice by ELISA

[0205] Method is detected with ELISA in embodiment 2, and the results are shown in Figure 7 A, 7B, 8A, 8B.

[0206] 2. Blood pressure telemetry in mice

[0207] Method is the same as blood pressure detection in embodiment 2, and the results are shown in Figure 7 C, 8C.

[0208] 2. Immunofluorescence detection of active oxygen content in tissues

[0209] Method is with the immunofluorescence detection in embodiment 2, and the results are shown in Figure 7 D, 8D.

[0210] 3. Treatment of mice with TNFa neutralizing antibody

[0211] 18-month-old WT and TDP1KO mice were treated with etanercept, a neutralizing antibody against TNFa, and the control group was tre...

Embodiment 4

[0213] Example 4 The DP1 agonist BW245C can significantly reduce the aging-related blood pressure increase in mice.

[0214] The main experimental parts involved in this embodiment are as follows:

[0215] 1. Treatment of mice with DP1 agonist

[0216] 18-month-old WT mice were treated with DP1 agonist BW245C, and the control group was treated with PBS. The agonist (1 mg / kg) was given by intraperitoneal injection twice a day until the seventh day of treatment, when blood pressure was monitored.

[0217] 2. Blood pressure telemetry in mice

[0218] Method is the same as blood pressure detection in embodiment 2, and the results are shown in Figure 9 A, 9B.

[0219] 3. RT-PCR detection of Th1 gene expression

[0220] Method is with the PCR detection of embodiment 1 cytokine, and the results are shown in Figure 9 C. Figure 9 d.

[0221] 4. Immunofluorescence detection of active oxygen content in tissues

[0222] Method is with the immunofluorescence detection in embodi...

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Abstract

The invention is clinically and repeatedly researched at the animal level, and it is found that in the occurrence and development process of senile-related hypertension, a prostaglandin D2 receptor DP1 inhibits generation of active oxygen and vascular remodeling by inhibiting Th1 type inflammatory reaction, and therefore the disease of hypertension is reduced; and after DP1 is activated, the disease of senile hypertension can be relieved. The content of basic research on the pathogenesis of the senile hypertension is enriched, and a new thought is provided for more deeply exploring the essential cause of the senile hypertension. Meanwhile, DP1 can serve as a new drug target for clinically treating the senile hypertension, and a DP1 agonist and a neutralizing antibody of Th1 type cytokinescan be referred to as potential drugs for treating the senile hypertension.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to DP1 as an immunotherapy drug target for senile hypertension and its application. Background technique [0002] Hypertension is a common disease in the elderly, and the number of elderly hypertensive patients is increasing year by year. According to the 2002 National Survey on Nutrition and Health of Residents, the prevalence of hypertension among adults in my country is 18.8%, while that of middle-aged and elderly people is as high as 39%. Innate immunity and adaptive immunity play an important role in the pathological process of hypertension. There is a close relationship between abnormal immune function and the occurrence and development of hypertension. Immune factors are widely involved in the regulation of blood pressure and affect each other. More and more studies have shown that T cells are mainly involved in AngⅡ-induced blood pressure elevation and vascular inju...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P9/12
CPCA61K45/00A61P9/12
Inventor 余鹰孔德平万强友
Owner TIANJIN MEDICAL UNIV
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