Establishment of basic laboratory model to evaluate TRP chanels and microcirculation on lower urinary tract

• Project/Area Number: 16K20129
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Shinshu University
• Principal Investigator: Minagawa Tomonori 信州大学, 学術研究院医学系(医学部附属病院), 講師 (60638873)
• Project Period (FY): 2016-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 下部尿路症状 / 微小循環 / TRP チャンネル / 漢方薬 / 膀胱 / 下部尿路機能 / 虚血 / 炎症 / TRPチャンネル / 血流障害 / TRP受容体 / 下部尿路 / 微小循環障害 / ニコチン / 冷えストレス / PDE5阻害剤 / 排尿機能学

Outline of Final Research Achievements

Choreito (CRT) is widely used for the treatment of overactive bladder (OAB) and other lower urinary tract symptoms in Japan. This study aimed to identify the effects and therapeutic mechanism of CRT on the improvement of detrusor overactivity (DO) using an experimental rat model. Sprague-Dawley rats were equally divided into three groups: intravesical saline instillation with normal food (normal group), intravesical acetic acid (AA) instillation with normal food (AA group), and intravesical AA instillation with CRT (AA with CRT group). Cystometric investigation and microcirculation was performed using a laser blood flowmeter. CRT attenuated decrease effect of AA about the bladder capacities. CRT might impart therapeutic effects on OAB via the mitigation of urothelial damage and regulation of excess blood flow.

Academic Significance and Societal Importance of the Research Achievements

猪苓湯は日本で一般的な漢方薬である。今回、TRPチャンネルを障害すると思われる酢酸での障害モデルに対して、猪苓湯は軽減させる効果があることが示された。微小循環の改善を経由して発揮された効果と考えられ、組織内の虚血改善に寄与したと考えられる。微小循環障害は、下部尿路障害を理解するうえで、非常に重要な病理である。微小循環障害に起因するさまざまな病態（過活動膀胱や尿失禁）に対して、猪苓湯が有効である可能性が示唆され、また、実験系によりそれが評価できることも示されたので、今後の研究発展につながると考えられる。

Research Products

• [Journal Article] Therapeutic effects of Choreito, a traditional Japanese (Kampo) medicine, on detrusor overactivity induced by acetic acid in rats (2020)
  • Author(s): Ueno Manabu、Minagawa Tomonori、Saito Tetsuichi、Imamura Tetsuya、Nagai Takashi、Ogawa Teruyuki、Ishizuka Osamu
  • Journal Title: LUTS: Lower Urinary Tract Symptoms Volume: 12 Issue: 3 Pages: 198-205
  • DOI: 10.1111/luts.12302
  • Peer Reviewed / Open Access
• [Journal Article] Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-Injured Rat Bladders (2018)
  • Author(s): Imamura T, Shimamura M, Ogawa T, Minagawa T, Nagai T, Silwal Gautam S, Ishizuka O
  • Journal Title: Tissue Eng Part A Volume: 24 Pages: 1574-1587
  • NAID: 120007099780
  • Peer Reviewed
• [Journal Article] Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats (2017)
  • Author(s): Imamura T, Ogawa T, Minagawa T, Nagai T, Suzuki T, Saito T, Yokoyama H, Nakazawa M, Ishizuka O
  • Journal Title: Neurourol Urodyn Volume: 36 Issue: 4 Pages: 1026-1033
  • DOI: 10.1002/nau.23061
  • Peer Reviewed / Open Access
• [Journal Article] Impact of ao-dake-humi, Japanese traditional bamboo foot stimulator, on lower urinary tract symptoms, constipation and hypersensitivity to cold: a single-arm prospective pilot study (2016)
  • Author(s): Minagawa T, Saitou T, Suzuki T, Domen T, Yokoyama H, Ishikawa M, Hirakata S, Nagai T, Nakazawa M, Ogawa T, Ishizuka O
  • Journal Title: BMC Complement Altern Med Volume: 16 Issue: 1 Pages: 513-513
  • DOI: 10.1186/s12906-016-1494-1
  • Peer Reviewed
• [Journal Article] Modified sonourethrography assists urethral catheterization (2016)
  • Author(s): Minagawa T, Suzuki T, Domen T, Yokoyama H, Ishikawa M, Hirakata S, Nagai T, Nakazawa M, Ogawa T, Ishizuka O
  • Journal Title: J Med Ultrason Volume: 43 Issue: 3 Pages: 443-448
  • DOI: 10.1007/s10396-016-0699-8
  • Peer Reviewed
• [Presentation] ニコチン投与がもたらす膀胱血流低下は尿路上皮で、
より低酸素化をきたし、機能的構造的影響を受ける (2018)
  • Author(s): 永井崇 今村哲也 上野学 鈴木都史郎 道面尚久 皆川倫範 小川輝之 石塚修
  • Organizer: 第25回日本排尿機能学会
• [Presentation] ニコチンは膀胱における尿路上皮の低酸素化とバリア機能の変化をもたらし頻尿をきたす (2018)
  • Author(s): 永井崇 今村哲也 上野学 鈴木都史郎 齊藤徹一 皆川倫範 道面尚久 小川典之 竹田裕 小川輝之 石塚修
  • Organizer: 第106回日本泌尿器科学会総会
• [Presentation] ニコチンは膀胱における尿路上皮の低酸素化とバリア機能の変化をもたらし頻尿をきたす (2018)
  • Author(s): 永井崇、今村哲也、上野学、鈴木都史郎、斎藤徹一、皆川倫範、道面尚久、小川典之、竹田裕、小川輝之、石塚修
  • Organizer: 第106回日本泌尿器科学会総会
• [Presentation] 青竹踏みの下部尿路症状・冷え・便秘・睡眠に及ぼす治療効果 (2017)
  • Author(s): 皆川倫範、小川輝之、石塚修
  • Organizer: 第105回日本泌尿器科学会総会
  • Place of Presentation: 城山観光ホテル、かごしま県民交流センター、宝山ホール
  • Year and Date: 2017-04-21
• [Presentation] Impact of Dai-ken-chu-tou on urinary frequency induced by cold stress in rats. American Urological Associstion. (2017)
  • Author(s): 斎藤徹一、皆川倫範、今村哲也、永井崇、小川輝之、石塚修
  • Organizer: American Urological Associstion. 2017/5/13, Boston USA
  • Int'l Joint Research
• [Presentation] 尿失禁治療における標準的保存療法とオプション～プロピベリン塩酸塩の新たな役割～ (2016)
  • Author(s): 皆川倫範
  • Organizer: 第23回日本排尿機能学会
  • Place of Presentation: 東京、東京国際フォーラム
  • Year and Date: 2016-12-06
  • Invited
• [Presentation] 信州大学における超音波検査～解剖・病態を理解し患者の安全を確保する～ (2016)
  • Author(s): 皆川倫範
  • Organizer: 第81回日本泌尿器科学会東部総会
  • Place of Presentation: 青森、リンクステーションホール青森、ホテル青森
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] Therapeutic effect of propiverine hydrochloride on mixed-type urinary incontinence in female. the Female Urgency and Stress Urinary Incontinence Study of Propiverine Hydrochloride (FRESH trial) (2016)
  • Author(s): Tomonori MINAGAWA, Momokazu GOTOH, Osamu YOKOYAMA, Kimio SUGAYA, Takashi KIKUCHI, Tomonori YAMANISHI, Kazuya KAWAHARA, Kanya KAGA, Emiko UNO, Kouichi YAMASHIRO, Osamu NISHIZAWA, and on behalf of the FRESH study group.
  • Organizer: Nagoya-Shinshu-Forlum 2016
  • Place of Presentation: Tokyo, FUKURACIA Tokyo station
  • Year and Date: 2016-09-17
  • Int'l Joint Research / Invited
• [Presentation] Impact of ao-dake-humi, Japanese traditional bamboo foot stimulator, on lower urinary tract symptoms, constipation, and hypersensitivity to cold: a single-arm prospective pilot study (2016)
  • Author(s): Tomonori MINAGAWA, Tetsuichi SAITOU, Takahisa DOMEN, Hitoshi YOKOYAMA, Masakuni ISHIKAWA, Shiro HIRAKATA, Takashi NAGAI, Masaki NAKAZAWA, Teruyuki OGAWA, Osamu ISHIZUKA.
  • Organizer: International continence society, annual meeting 2016
  • Place of Presentation: Tokyo International Forum
  • Year and Date: 2016-09-13
• [Presentation] Therapeutic effects of propiverine hydrochloride on mix-type urinary incontinence in female:a multicenter, single arm and open label study (2016)
  • Author(s): Tomonori MINAGAWA, , Momokazu GOTOH, Osamu YOKOYAMA, Kimio SUGAYA, Takashi KIKUCHI, Tomonori YAMANISHI, Kazuya KAWAHARA, Kanya KAGA, Emiko UNO, Kouichi YAMASHIRO, Osamu NISHIZAWA, and on behalf of the FRESH study group
  • Organizer: International continence society, annual meeting 2016
  • Place of Presentation: Tokyo International Forum
  • Year and Date: 2016-09-13